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class="vector-toc-list"> <li id="toc-Types" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Types"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.1</span> <span>Types</span> </div> </a> <ul id="toc-Types-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Inorganic_adjuvants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Inorganic_adjuvants"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.2</span> <span>Inorganic adjuvants</span> </div> </a> <ul id="toc-Inorganic_adjuvants-sublist" class="vector-toc-list"> <li id="toc-Aluminium_salts" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Aluminium_salts"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.2.1</span> <span>Aluminium salts</span> </div> </a> <ul id="toc-Aluminium_salts-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Organic_adjuvants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Organic_adjuvants"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.3</span> <span>Organic adjuvants</span> </div> </a> <ul id="toc-Organic_adjuvants-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Adaptive_immune_response" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Adaptive_immune_response"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Adaptive immune response</span> </div> </a> <ul id="toc-Adaptive_immune_response-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Toll-like_receptors" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Toll-like_receptors"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Toll-like receptors</span> </div> </a> <ul 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interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Adyuvante_inmunol%C3%B3gico" title="Adyuvante inmunológico – Spanish" lang="es" hreflang="es" data-title="Adyuvante inmunológico" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Adjuvant_immunologique" title="Adjuvant immunologique – French" lang="fr" hreflang="fr" data-title="Adjuvant immunologique" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EB%A9%B4%EC%97%AD%ED%95%99%EC%A0%81_%EB%B3%B4%EC%A1%B0%EC%A0%9C" title="면역학적 보조제 – Korean" lang="ko" hreflang="ko" data-title="면역학적 보조제" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Adjuvan_imunologis" title="Adjuvan imunologis – Indonesian" lang="id" hreflang="id" data-title="Adjuvan imunologis" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Adiuvante_(immunologia)" title="Adiuvante (immunologia) – Italian" lang="it" hreflang="it" data-title="Adiuvante (immunologia)" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Immunologisch_adjuvant" title="Immunologisch adjuvant – Dutch" lang="nl" hreflang="nl" data-title="Immunologisch adjuvant" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/Immunologisk_adjuvant" title="Immunologisk adjuvant – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Immunologisk adjuvant" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target"><span>Norsk bokmål</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Adiuwant_(immunologia)" title="Adiuwant (immunologia) – Polish" lang="pl" hreflang="pl" data-title="Adiuwant (immunologia)" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Adjuvante_imunol%C3%B3gico" title="Adjuvante imunológico – Portuguese" lang="pt" hreflang="pt" data-title="Adjuvante imunológico" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-sk mw-list-item"><a href="https://sk.wikipedia.org/wiki/Adjuvans_(imunol%C3%B3gia)" title="Adjuvans (imunológia) – Slovak" lang="sk" hreflang="sk" data-title="Adjuvans (imunológia)" data-language-autonym="Slovenčina" data-language-local-name="Slovak" class="interlanguage-link-target"><span>Slovenčina</span></a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/%C4%B0mm%C3%BCnolojik_adjuvan" title="İmmünolojik adjuvan – Turkish" lang="tr" hreflang="tr" data-title="İmmünolojik adjuvan" data-language-autonym="Türkçe" data-language-local-name="Turkish" class="interlanguage-link-target"><span>Türkçe</span></a></li><li class="interlanguage-link interwiki-zh mw-list-item"><a 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<div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Component of vaccines</div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">For other uses, see <a href="/wiki/Adjuvant" title="Adjuvant">adjuvant</a>.</div> <p> In <a href="/wiki/Immunology" title="Immunology">immunology</a>, an <b>adjuvant</b> is a substance that increases or modulates the immune response to a <a href="/wiki/Vaccine" title="Vaccine">vaccine</a>.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> The word "adjuvant" comes from the Latin word <span title="Latin-language text"><i lang="la">adiuvare</i></span>, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine <a href="/wiki/Antigen" title="Antigen">antigens</a>."<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>In the early days of vaccine manufacture, significant variations in the efficacy of different batches of the same vaccine were correctly assumed to be caused by contamination of the reaction vessels. However, it was soon found that more scrupulous cleaning actually seemed to <i>reduce</i> the effectiveness of the vaccines, and some contaminants actually enhanced the immune response. </p><p>There are many known adjuvants in widespread use, including <a href="/w/index.php?title=Aluminium_salt&action=edit&redlink=1" class="new" title="Aluminium salt (page does not exist)">aluminium salts</a>, oils and <a href="/wiki/Virosome" title="Virosome">virosomes</a>.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p> <style data-mw-deduplicate="TemplateStyles:r886046785">.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 ul{display:none}</style><div class="toclimit-3"><meta property="mw:PageProp/toc" /></div> <div class="mw-heading mw-heading2"><h2 id="Overview">Overview</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=1" title="Edit section: Overview"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Adjuvants in <a href="/wiki/Immunology" title="Immunology">immunology</a> are often used to modify or augment the effects of a vaccine by stimulating the <a href="/wiki/Immune_system" title="Immune system">immune system</a> to <a href="/wiki/Immune_response" title="Immune response">respond</a> to the vaccine more vigorously, and thus providing increased immunity to a particular <a href="/wiki/Disease" title="Disease">disease</a>. Adjuvants accomplish this task by mimicking specific sets of <a href="/wiki/Evolutionarily" class="mw-redirect" title="Evolutionarily">evolutionarily</a> conserved molecules, so called <a href="/wiki/Pathogen-associated_molecular_pattern" title="Pathogen-associated molecular pattern">pathogen-associated molecular patterns</a>, which include <a href="/wiki/Liposomes" class="mw-redirect" title="Liposomes">liposomes</a>, <a href="/wiki/Lipopolysaccharide" title="Lipopolysaccharide">lipopolysaccharide</a>, molecular cages for <a href="/wiki/Antigen" title="Antigen">antigens</a>, components of bacterial <a href="/wiki/Cell_walls" class="mw-redirect" title="Cell walls">cell walls</a>, and <a href="/wiki/Endocytosis" title="Endocytosis">endocytosed</a> nucleic acids such as <a href="/wiki/RNA" title="RNA">RNA</a>, <a href="/wiki/DsRNA" class="mw-redirect" title="DsRNA">double-stranded RNA</a>, <a href="/wiki/SsDNA" class="mw-redirect" title="SsDNA">single-stranded DNA</a>, and <a href="/wiki/CpG_Oligodeoxynucleotide" class="mw-redirect" title="CpG Oligodeoxynucleotide">unmethylated CpG</a> dinucleotide-containing DNA.<sup id="cite_ref-Gavin_4-0" class="reference"><a href="#cite_note-Gavin-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Because immune systems have <a href="/wiki/Evolved" class="mw-redirect" title="Evolved">evolved</a> to recognize these specific <a href="/wiki/Antigenic" class="mw-redirect" title="Antigenic">antigenic</a> <a href="/wiki/Moiety_(chemistry)" title="Moiety (chemistry)">moieties</a>, the presence of an adjuvant in conjunction with the vaccine can greatly increase the <a href="/wiki/Innate_immune_response" class="mw-redirect" title="Innate immune response">innate immune response</a> to the antigen by augmenting the activities of <a href="/wiki/Dendritic_cells" class="mw-redirect" title="Dendritic cells">dendritic cells</a>, <a href="/wiki/Lymphocytes" class="mw-redirect" title="Lymphocytes">lymphocytes</a>, and <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a> by mimicking a natural <a href="/wiki/Infection" title="Infection">infection</a>.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Types">Types</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=2" title="Edit section: Types"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li>Inorganic compounds: <a href="/wiki/Potassium_alum" title="Potassium alum">potassium alum</a>, <a href="/wiki/Aluminium_hydroxide" title="Aluminium hydroxide">aluminium hydroxide</a>, <a href="/wiki/Aluminium_phosphate" title="Aluminium phosphate">aluminium phosphate</a>,<sup id="cite_ref-Guimarães_7-0" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Hydroxyapatite" title="Hydroxyapatite">calcium phosphate hydroxide</a></li> <li>Oils: <a href="/wiki/Liquid_paraffin_(medicinal)" class="mw-redirect" title="Liquid paraffin (medicinal)">paraffin oil</a>,<sup id="cite_ref-Guimarães_7-1" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Propolis" title="Propolis">propolis</a> (only in <a href="/wiki/Preclinical_studies" class="mw-redirect" title="Preclinical studies">preclinical studies</a>).<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Adjuvant 65 (based on <a href="/wiki/Peanut_oil" title="Peanut oil">peanut oil</a>)<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> was tested in influenza vaccines in the 1970s, but was never released commercially.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> The oil <a href="/wiki/Squalene" title="Squalene">squalene</a><sup id="cite_ref-Guimarães_7-2" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> is used in the adjuvant <a href="/wiki/MF59" title="MF59">MF59</a>.<sup id="cite_ref-Pulendran_2021_11-0" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup></li> <li>Bacterial products: killed bacteria of the species <i><a href="/wiki/Bordetella_pertussis" title="Bordetella pertussis">Bordetella pertussis</a></i>, <i><a href="/wiki/Mycobacterium_bovis" title="Mycobacterium bovis">Mycobacterium bovis</a></i>,<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (February 2021)">citation needed</span></a></i>]</sup> <a href="/wiki/Toxoid" title="Toxoid">toxoids</a>.<sup id="cite_ref-Guimarães_7-3" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> MPL (Monophosphorylated lipid A) is a modified form of a bacterial <a href="/wiki/Lipid_A" title="Lipid A">lipid A</a> protein that is used in several vaccines.</li> <li>Plant <a href="/wiki/Saponin" title="Saponin">saponins</a> from <a href="/wiki/Quillaia" title="Quillaia">Quillaia</a> (the bark of a soap bark tree),<sup id="cite_ref-Guimarães_7-4" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Soybean" title="Soybean">soybean</a>, <i><a href="/wiki/Polygala_senega" class="mw-redirect" title="Polygala senega">Polygala senega</a></i></li> <li>Cytokines: <a href="/wiki/Interleukin_1" class="mw-redirect" title="Interleukin 1">IL-1</a>, <a href="/wiki/Interleukin_2" title="Interleukin 2">IL-2</a>, <a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a></li> <li><a href="/wiki/CpG_site" title="CpG site">CpG</a> <a href="/wiki/Oligonucleotide" title="Oligonucleotide">oligonucleotides</a></li> <li>Combinations: <a href="/wiki/Freund%27s_adjuvant" title="Freund's adjuvant">Freund's complete adjuvant</a>, Freund's incomplete adjuvant,<sup id="cite_ref-Guimarães_7-5" class="reference"><a href="#cite_note-Guimarães-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> AS01 (combining MPL and Quillaia saponins),<sup id="cite_ref-Pulendran_2021_11-1" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Matrix-M" title="Matrix-M">Matrix-M</a> (combining Quillaia saponins and two types of fat)</li> <li>Small molecules: TLR7/8 agonists (imidazoquinolines,<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> imidazopyrimidines<sup id="cite_ref-From_hit_to_vial:_Precision_discove_13-0" class="reference"><a href="#cite_note-From_hit_to_vial:_Precision_discove-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup>)</li></ul> <div class="mw-heading mw-heading3"><h3 id="Inorganic_adjuvants">Inorganic adjuvants</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=3" title="Edit section: Inorganic adjuvants"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading4"><h4 id="Aluminium_salts">Aluminium salts</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=4" title="Edit section: Aluminium salts"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are many adjuvants, some of which are <a href="/wiki/Inorganic" class="mw-redirect" title="Inorganic">inorganic</a>, that carry the potential to augment <a href="/wiki/Immunogenicity" title="Immunogenicity">immunogenicity</a>.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Potassium_alum" title="Potassium alum">Alum</a> was the first aluminium <a href="/wiki/Salt_(chemistry)" title="Salt (chemistry)">salt</a> used for this purpose, but has been almost completely replaced by <a href="/wiki/Aluminium_hydroxide" title="Aluminium hydroxide">aluminium hydroxide</a> and <a href="/wiki/Aluminium_phosphate" title="Aluminium phosphate">aluminium phosphate</a> for commercial vaccines.<sup id="cite_ref-Marrack2009_16-0" class="reference"><a href="#cite_note-Marrack2009-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> Aluminium salts are the most commonly-used adjuvants in human vaccines. Their adjuvant activity was described in 1926.<sup id="cite_ref-Apostolico-rev_17-0" class="reference"><a href="#cite_note-Apostolico-rev-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>The precise mechanism of aluminium salts remains unclear but some insights have been gained. It was formerly thought that they function as delivery systems by generating depots that trap antigens at the injection site, providing a slow release that continues to stimulate the immune system.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> However, studies have shown that surgical removal of these depots had no impact on the magnitude of <a href="/wiki/Immunoglobulin_G" title="Immunoglobulin G">IgG1</a> response.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>Alum can trigger <a href="/wiki/Dendritic_cell" title="Dendritic cell">dendritic cells</a> and other immune cells to secrete <a href="/wiki/Interleukin_1_beta" title="Interleukin 1 beta">Interleukin 1 beta</a> (IL‑1β), an immune signal that promotes antibody production. Alum adheres to the cell's plasma membrane and rearranges certain lipids there. Spurred into action, the dendritic cells pick up the antigen and speed to lymph nodes, where they stick tightly to a <a href="/wiki/Helper_T_cell" class="mw-redirect" title="Helper T cell">helper T cell</a> and presumably induce an immune response. A second mechanism depends on alum killing immune cells at the injection site although researchers aren't sure exactly how alum kills these cells. It has been speculated that the dying cells release DNA which serves as an immune alarm. Some studies found that DNA from dying cells causes them to adhere more tightly to helper T cells which ultimately leads to an increased release of antibodies by <a href="/wiki/B_cells" class="mw-redirect" title="B cells">B cells</a>. No matter what the mechanism is, alum is not a perfect adjuvant because it does not work with all antigens (e.g. malaria and tuberculosis).<sup id="cite_ref-pmid23828925_20-0" class="reference"><a href="#cite_note-pmid23828925-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> However, recent research indicates that alum formulated in a <a href="/wiki/Nanoparticle" title="Nanoparticle">nanoparticle</a> form rather than microparticles can broaden the utility of alum adjuvants and promote stronger adjuvant effects.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Organic_adjuvants">Organic adjuvants</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=5" title="Edit section: Organic adjuvants"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Freund%27s_adjuvant" title="Freund's adjuvant">Freund's complete adjuvant</a> is a solution of inactivated <i><a href="/wiki/Mycobacterium_tuberculosis" title="Mycobacterium tuberculosis">Mycobacterium tuberculosis</a></i> in mineral oil developed in 1930. It is not safe enough for human use. A version without the bacteria, that is only oil in water, is known as Freund's incomplete adjuvant. It helps vaccines release antigens for a longer time. Despite the side effects, its potential benefit has led to a few clinical trials.<sup id="cite_ref-Apostolico-rev_17-1" class="reference"><a href="#cite_note-Apostolico-rev-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Squalene" title="Squalene">Squalene</a> is a naturally-occurring organic compound used in human and animal vaccines. Squalene is an oil, made up of carbon and hydrogen atoms, produced by plants and is present in many foods. Squalene is also produced by the human liver as a precursor to <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> and is present in human <a href="/wiki/Sebum" class="mw-redirect" title="Sebum">sebum</a>.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> <a href="/wiki/MF59" title="MF59">MF59</a> is an oil-in-water emulsion of squalene adjuvant used in some human vaccines. As of 2021, over 22 million doses of one vaccine with squalene, FLUAD, have been administered with no severe adverse effects reported.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> <a href="/wiki/AS03" title="AS03">AS03</a> is another squalene-containing adjuvant.<sup id="cite_ref-emea_24-0" class="reference"><a href="#cite_note-emea-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> In addition, squalene-based O/W emulsions have also been shown to stably incorporate small molecule TLR7/8 adjuvants (e.g. PVP-037) and lead to enhanced adjuvanticity via synergism.<sup id="cite_ref-From_hit_to_vial:_Precision_discove_13-1" class="reference"><a href="#cite_note-From_hit_to_vial:_Precision_discove-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p><p>The plant extract <a href="/wiki/QS-21" title="QS-21">QS-21</a> is a liposome made up of two plant <a href="/wiki/Saponin" title="Saponin">saponins</a> from <i><a href="/wiki/Quillaja_saponaria" title="Quillaja saponaria">Quillaja saponaria</a></i>, a Chilean soap bark tree.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Stertman_2023_26-0" class="reference"><a href="#cite_note-Stertman_2023-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p><p>Monophosphoryl <a href="/wiki/Lipid_A" title="Lipid A">lipid A</a> (MPL), a detoxified version of the <a href="/wiki/Lipopolysaccharide" title="Lipopolysaccharide">lipopolysaccharide</a> from the bacterium <a href="/wiki/Salmonella_enterica_subsp._enterica" title="Salmonella enterica subsp. enterica"><i>Salmonella</i> Minnesota</a>, interacts with the receptor <a href="/wiki/TLR4" class="mw-redirect" title="TLR4">TLR4</a> to enhance immune response.<sup id="cite_ref-Shingrix_27-0" class="reference"><a href="#cite_note-Shingrix-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Apostolico-rev_17-2" class="reference"><a href="#cite_note-Apostolico-rev-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>The combination of QS-21, cholesterol and MPL forms the adjuvant AS01<sup id="cite_ref-Pulendran_2021_11-2" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> which is used in the <a href="/wiki/Shingrix" class="mw-redirect" title="Shingrix">Shingrix</a> vaccine approved in 2017,<sup id="cite_ref-Shingrix_27-1" class="reference"><a href="#cite_note-Shingrix-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> as well as in the approved <a href="/wiki/Malaria_vaccine" title="Malaria vaccine">malaria vaccine</a> <a href="/wiki/RTS,S" title="RTS,S">Mosquirix</a>.<sup id="cite_ref-Pulendran_2021_11-3" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p><p>The adjuvant <a href="/wiki/Matrix-M" title="Matrix-M">Matrix-M</a> is an <a href="/wiki/ISCOM" title="ISCOM">immune stimulating complex</a> (ISCOM) consisting of nanospheres made of QS-21, <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a> and <a href="/wiki/Phospholipid" title="Phospholipid">phospholipids</a>.<sup id="cite_ref-Stertman_2023_26-1" class="reference"><a href="#cite_note-Stertman_2023-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> It is used in the approved <a href="/wiki/Novavax_COVID-19_vaccine" title="Novavax COVID-19 vaccine">Novavax Covid-19 vaccine</a> and in the <a href="/wiki/Malaria_vaccine" title="Malaria vaccine">malaria vaccine</a> R21/Matrix-M. </p><p>Several unmethylated <a href="/wiki/CpG_site" title="CpG site">cytosine phosphoguanosine</a> (CpG) <a href="/wiki/Oligonucleotide" title="Oligonucleotide">oligonucleotides</a> activate the <a href="/wiki/Tlr9" class="mw-redirect" title="Tlr9">TLR9</a> receptor that is present in a number of cell types of the immune system. The adjuvant CpG 1018 is used in an approved <a href="/wiki/Hepatitis_B_vaccine" title="Hepatitis B vaccine">Hepatitis B vaccine</a>.<sup id="cite_ref-Pulendran_2021_11-4" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Adaptive_immune_response">Adaptive immune response</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=6" title="Edit section: Adaptive immune response"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In order to understand the links between the innate immune response and the adaptive immune response to help substantiate an adjuvant function in enhancing adaptive immune responses to the specific antigen of a vaccine, the following points should be considered: </p> <ul><li>Innate immune response cells such as <a href="/wiki/Dendritic_cell" title="Dendritic cell">dendritic cells</a> engulf <a href="/wiki/Pathogens" class="mw-redirect" title="Pathogens">pathogens</a> through a process called <a href="/wiki/Phagocytosis" title="Phagocytosis">phagocytosis</a>.</li> <li>Dendritic cells then migrate to the <a href="/wiki/Lymph_nodes" class="mw-redirect" title="Lymph nodes">lymph nodes</a> where <a href="/wiki/T_cells" class="mw-redirect" title="T cells">T cells</a> (adaptive immune cells) wait for signals to trigger their activation.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup></li> <li>In the lymph nodes, dendritic cells mince the engulfed pathogen and then express the pathogen clippings as antigen on their <a href="/wiki/Cell_(biology)" title="Cell (biology)">cell</a> surface by coupling them to a special receptor known as a <a href="/wiki/Major_histocompatibility_complex" title="Major histocompatibility complex">major histocompatibility complex</a>.</li> <li>T cells can then recognize these clippings and undergo a <a href="/wiki/Cellular_transformation" class="mw-redirect" title="Cellular transformation">cellular transformation</a> resulting in their own activation.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/%CE%93%CE%B4_T_cells" class="mw-redirect" title="Γδ T cells">γδ T cells</a> possess characteristics of both the innate and adaptive immune responses.</li> <li><a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">Macrophages</a> can also activate T cells in a similar approach (but do not do so naturally).</li></ul> <p>This process carried out by both dendritic cells and macrophages is termed <a href="/wiki/Antigen_presentation" title="Antigen presentation">antigen presentation</a> and represents a physical link between the innate and adaptive immune responses. </p><p>Upon activation, <a href="/wiki/Mast_cells" class="mw-redirect" title="Mast cells">mast cells</a> release <a href="/wiki/Heparin" title="Heparin">heparin</a> and <a href="/wiki/Histamine" title="Histamine">histamine</a> to effectively increase trafficking to and seal off the site of <a href="/wiki/Infection" title="Infection">infection</a> to allow immune cells of both systems to clear the area of pathogens. In addition, mast cells also release <a href="/wiki/Chemokines" class="mw-redirect" title="Chemokines">chemokines</a> which result in the positive <a href="/wiki/Chemotaxis" title="Chemotaxis">chemotaxis</a> of other immune cells of both the innate and adaptive immune responses to the infected area.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> </p><p>Due to the variety of mechanisms and links between the innate and adaptive immune response, an adjuvant-enhanced innate immune response results in an enhanced adaptive immune response. Specifically, adjuvants may exert their immune-enhancing effects according to five immune-functional activities.<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p> <ul><li>First, adjuvants may help in the translocation of <a href="/wiki/Antigens" class="mw-redirect" title="Antigens">antigens</a> to the <a href="/wiki/Lymph_nodes" class="mw-redirect" title="Lymph nodes">lymph nodes</a> where they can be recognized by <a href="/wiki/T_cells" class="mw-redirect" title="T cells">T cells</a>. This will ultimately lead to greater T cell activity resulting in a heightened <a href="/wiki/Clearance_(medicine)" class="mw-redirect" title="Clearance (medicine)">clearance</a> of <a href="/wiki/Pathogen" title="Pathogen">pathogen</a> throughout the <a href="/wiki/Organism" title="Organism">organism</a>.</li> <li>Second, adjuvants may provide physical protection to antigens which grants the antigen a prolonged delivery. This means the organism will be exposed to the antigen for a longer duration, making the immune system more <a href="https://en.wiktionary.org/wiki/robust" class="extiw" title="wikt:robust">robust</a> as it makes use of the additional time by upregulating the production of B and T cells needed for greater immunological <a href="/wiki/Memory" title="Memory">memory</a> in the adaptive immune response.</li> <li>Third, adjuvants may help to increase the capacity to cause local reactions at the <a href="/wiki/Injection_(medicine)" title="Injection (medicine)">injection</a> site (during vaccination), inducing greater release of danger signals by <a href="/wiki/Chemokine" title="Chemokine">chemokine</a> releasing cells such as <a href="/wiki/Helper_T_cells" class="mw-redirect" title="Helper T cells">helper T cells</a> and mast cells.</li> <li>Fourth, they may induce the release of inflammatory cytokines which helps to not only recruit B and T cells at sites of <a href="/wiki/Infection" title="Infection">infection</a> but also to increase <a href="/wiki/Transcriptional" class="mw-redirect" title="Transcriptional">transcriptional</a> events leading to a net increase of <a href="/wiki/Immune_cells" class="mw-redirect" title="Immune cells">immune cells</a> as a whole.</li> <li>Finally, adjuvants are believed to increase the innate immune response to antigen by interacting with <a href="/wiki/Pattern_recognition_receptors" class="mw-redirect" title="Pattern recognition receptors">pattern recognition receptors</a> (PRRs) on or within accessory cells.<sup id="cite_ref-Pulendran_2021_11-5" class="reference"><a href="#cite_note-Pulendran_2021-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup></li></ul> <div class="mw-heading mw-heading2"><h2 id="Toll-like_receptors">Toll-like receptors</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=7" title="Edit section: Toll-like receptors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The ability of the immune system to recognize <a href="/wiki/Molecule" title="Molecule">molecules</a> that are broadly shared by <a href="/wiki/Pathogen" title="Pathogen">pathogens</a> is, in part, due to the presence of <a href="/wiki/Immune_receptor" title="Immune receptor">immune receptors</a> called <a href="/wiki/Toll-like_receptors" class="mw-redirect" title="Toll-like receptors">toll-like receptors</a> (TLRs) that are expressed on the <a href="/wiki/Cell_membrane" title="Cell membrane">membranes</a> of <a href="/wiki/Leukocyte" class="mw-redirect" title="Leukocyte">leukocytes</a> including <a href="/wiki/Dendritic_cells" class="mw-redirect" title="Dendritic cells">dendritic cells</a>, <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>, <a href="/wiki/Natural_killer_cells" class="mw-redirect" title="Natural killer cells">natural killer cells</a>, cells of the adaptive immunity (T and B lymphocytes) and non-immune cells (<a href="/wiki/Epithelial" class="mw-redirect" title="Epithelial">epithelial</a> and <a href="/wiki/Endothelial_cells" class="mw-redirect" title="Endothelial cells">endothelial cells</a>, and <a href="/wiki/Fibroblasts" class="mw-redirect" title="Fibroblasts">fibroblasts</a>).<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p><p>The binding of <a href="/wiki/Ligands" class="mw-redirect" title="Ligands">ligands</a> – either in the form of adjuvant used in <a href="/wiki/Vaccinations" class="mw-redirect" title="Vaccinations">vaccinations</a> or in the form of invasive moieties during times of natural infection –  to TLRs mark the key <a href="/wiki/Molecular" class="mw-redirect" title="Molecular">molecular</a> events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Medzhitov_35-0" class="reference"><a href="#cite_note-Medzhitov-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p><p>As of 2016, several TLR ligands were in clinical development or being tested in animal models as potential adjuvants.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Medical_complications">Medical complications</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=8" title="Edit section: Medical complications"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Humans">Humans</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=9" title="Edit section: Humans"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Aluminium salts used in many human vaccines are regarded as safe by <a href="/wiki/Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a>.<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> Although there are studies suggesting the role of aluminium, especially injected highly <a href="/wiki/Bioavailable" class="mw-redirect" title="Bioavailable">bioavailable</a> antigen-aluminium complexes when used as adjuvant, in <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a> development,<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> the majority of researchers do not support a causal connection with aluminium.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> Adjuvants may make vaccines too <a href="/wiki/Reactogenicity" title="Reactogenicity">reactogenic</a>, which often leads to <a href="/wiki/Fever" title="Fever">fever</a>. This is often an expected outcome upon vaccination and is usually controlled in infants by <a href="/wiki/Over-the-counter_drug" title="Over-the-counter drug">over-the-counter</a> medication if necessary. </p><p>An increased number of <a href="/wiki/Narcolepsy" title="Narcolepsy">narcolepsy</a> (a chronic sleep disorder) cases in children and adolescents was observed in <a href="/wiki/Scandinavia" title="Scandinavia">Scandinavian</a> and other European countries after vaccinations to address the <a href="/wiki/H1N1" class="mw-redirect" title="H1N1">H1N1</a> "swine flu" <a href="/wiki/2009_flu_pandemic" class="mw-redirect" title="2009 flu pandemic">pandemic in 2009</a>. Narcolepsy has previously been associated with <a href="/wiki/Human_leukocyte_antigen" title="Human leukocyte antigen">HLA</a>-subtype DQB1*602, which has led to the prediction that it is an autoimmune process. After a series of epidemiological investigations, researchers found that the higher <a href="/wiki/Incidence_(epidemiology)" title="Incidence (epidemiology)">incidence</a> correlated with the use of AS03-adjuvanted influenza vaccine (<a href="/wiki/Pandemrix" title="Pandemrix">Pandemrix</a>). Those vaccinated with Pandemrix have almost a twelve-times higher risk of developing the disease.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> The adjuvant of the vaccine contained <a href="/wiki/Vitamin_E" title="Vitamin E">vitamin E</a> that was no more than a day's normal dietary intake. Vitamin E increases <a href="/wiki/Orexin" title="Orexin">hypocretin</a>-specific fragments that bind to DQB1*602 in cell culture experiments, leading to the hypothesis that autoimmunity may arise in genetically susceptible individuals,<sup id="cite_ref-Masoudi2014_42-0" class="reference"><a href="#cite_note-Masoudi2014-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> but there is no clinical data to support this hypothesis. The third AS03 ingredient is <a href="/wiki/Polysorbate_80" title="Polysorbate 80">polysorbate 80</a>.<sup id="cite_ref-emea_24-1" class="reference"><a href="#cite_note-emea-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> Polysorbate<span class="nowrap"> </span>80 is also found in both the <a href="/wiki/Oxford%E2%80%93AstraZeneca_COVID-19_vaccine" title="Oxford–AstraZeneca COVID-19 vaccine">Oxford–AstraZeneca</a> and <a href="/wiki/Janssen_COVID-19_vaccine" title="Janssen COVID-19 vaccine">Janssen</a> <a href="/wiki/COVID-19_vaccine" title="COVID-19 vaccine">COVID-19 vaccines</a>.<sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Animals">Animals</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=10" title="Edit section: Animals"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Aluminium adjuvants have caused motor neuron death in mice<sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> when injected directly onto the spine at the scruff of the neck, and oil–water suspensions have been reported to increase the risk of <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune disease</a> in mice.<sup id="cite_ref-46" class="reference"><a href="#cite_note-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> Squalene has caused <a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a> in rats already prone to arthritis.<sup id="cite_ref-47" class="reference"><a href="#cite_note-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> </p><p>In cats, <a href="/wiki/Vaccine-associated_sarcoma" title="Vaccine-associated sarcoma">vaccine-associated sarcoma</a> (VAS) occurs at a rate of 1–10 per 10,000 injections. In 1993, a <a href="/wiki/Causality" title="Causality">causal</a> relationship between VAS and administration of aluminium adjuvated rabies and FeLV vaccines was established through <a href="/wiki/Epidemiology" title="Epidemiology">epidemiologic</a> methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem.<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> However, evidence conflicts on whether types of vaccines, manufacturers or factors have been associated with sarcomas.<sup id="cite_ref-49" class="reference"><a href="#cite_note-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Controversy">Controversy</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=11" title="Edit section: Controversy"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="TLR_signaling">TLR signaling</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=12" title="Edit section: TLR signaling"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As of 2006<sup class="plainlinks noexcerpt noprint asof-tag update" style="display:none;"><a class="external text" href="https://en.wikipedia.org/w/index.php?title=Immunologic_adjuvant&action=edit">[update]</a></sup>, the premise that TLR signaling acts as the key node in antigen-mediated <a href="/wiki/Inflammation" title="Inflammation">inflammatory</a> responses has been in question as <a href="/wiki/Researchers" class="mw-redirect" title="Researchers">researchers</a> have observed antigen-mediated inflammatory responses in <a href="/wiki/Leukocytes" class="mw-redirect" title="Leukocytes">leukocytes</a> in the absence of TLR signaling.<sup id="cite_ref-Gavin_4-1" class="reference"><a href="#cite_note-Gavin-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-50" class="reference"><a href="#cite_note-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> One <a href="/wiki/Researcher" class="mw-redirect" title="Researcher">researcher</a> found that in the absence of <a href="/wiki/MyD88" class="mw-redirect" title="MyD88">MyD88</a> and <a href="/wiki/Trif" class="mw-redirect" title="Trif">Trif</a> (essential <a href="/wiki/Adapter" title="Adapter">adapter</a> proteins in TLR signaling), they were still able to induce inflammatory responses, increase T cell activation and generate greater <a href="/wiki/B_cell" title="B cell">B cell</a> abundancy using conventional adjuvants (<a href="/wiki/Alum" title="Alum">alum</a>, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate (<a href="/wiki/Polyclonal_antibodies#Ribi_Adjuvant_System" title="Polyclonal antibodies">Ribi's adjuvant</a>)).<sup id="cite_ref-Gavin_4-2" class="reference"><a href="#cite_note-Gavin-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p><p>These observations suggest that although TLR activation can lead to increases in antibody responses, TLR activation is not required to induce enhanced innate and adaptive responses to antigens. </p><p><a href="/wiki/Medical_research" title="Medical research">Investigating</a> the <a href="/wiki/Mechanism_(biology)" title="Mechanism (biology)">mechanisms</a> which underlie TLR signaling has been significant in understanding why adjuvants used during vaccinations are so important in augmenting adaptive immune responses to specific <a href="/wiki/Antigens" class="mw-redirect" title="Antigens">antigens</a>. However, with the knowledge that TLR activation is not required for the immune-enhancing effects caused by common adjuvants, we can conclude that there are, in all likelihood, other receptors besides TLRs that have not yet been characterized, opening the door to future research. </p> <div class="mw-heading mw-heading3"><h3 id="Safety">Safety</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=13" title="Edit section: Safety"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Reports after the first Gulf War linked anthrax vaccine adjuvants<sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> to <a href="/wiki/Gulf_War_syndrome" title="Gulf War syndrome">Gulf War syndrome</a> in American and British troops.<sup id="cite_ref-52" class="reference"><a href="#cite_note-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> The <a href="/wiki/United_States_Department_of_Defense" title="United States Department of Defense">United States Department of Defense</a> strongly denied the claims. </p><p>Discussing the safety of squalene as an adjuvant in 2006, the World Health Organisation stated "follow-up to detect any vaccine-related adverse events will need to be performed."<sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> No such followup has been published by the WHO. </p><p>Subsequently, the American National Center for Biotechnology Information published an article discussing the comparative safety of vaccine adjuvants which stated that "the biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions, such as narcolepsy, macrophagic myofasciitis or Alzheimer's disease."<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=14" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Beta-glucan" title="Beta-glucan">Beta-glucan</a></li> <li><a href="/wiki/Immunomodulator" class="mw-redirect" title="Immunomodulator">Immunomodulator</a></li> <li><a href="/wiki/Immunostimulant" title="Immunostimulant">Immunostimulant</a></li> <li><a href="/wiki/Pharmaceutic_adjuvant" class="mw-redirect" title="Pharmaceutic adjuvant">Pharmaceutic adjuvant</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=15" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003809.pdf">"Guideline on Adjuvants in Vaccines for Human Use"</a> <span class="cs1-format">(PDF)</span>. The European Medicines Agency. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20180614120140/http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003809.pdf">Archived</a> <span class="cs1-format">(PDF)</span> from the original on 14 June 2018<span class="reference-accessdate">. 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title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Drug+Safety&rft.atitle=Comparative+Safety+of+Vaccine+Adjuvants%3A+A+Summary+of+Current+Evidence+and+Future+Needs&rft.volume=38&rft.issue=11&rft.pages=1059-1074&rft.date=2015-11&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4615573%23id-name%3DPMC&rft_id=info%3Apmid%2F26446142&rft_id=info%3Adoi%2F10.1007%2Fs40264-015-0350-4&rft.aulast=Petrovsky&rft.aufirst=N&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4615573&rfr_id=info%3Asid%2Fen.wikipedia.org%3AImmunologic+adjuvant" class="Z3988"></span></span> </li> </ol></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Immunologic_adjuvant&action=edit&section=16" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1235681985">.mw-parser-output .side-box{margin:4px 0;box-sizing:border-box;border:1px solid #aaa;font-size:88%;line-height:1.25em;background-color:var(--background-color-interactive-subtle,#f8f9fa);display:flow-root}.mw-parser-output .side-box-abovebelow,.mw-parser-output .side-box-text{padding:0.25em 0.9em}.mw-parser-output .side-box-image{padding:2px 0 2px 0.9em;text-align:center}.mw-parser-output .side-box-imageright{padding:2px 0.9em 2px 0;text-align:center}@media(min-width:500px){.mw-parser-output .side-box-flex{display:flex;align-items:center}.mw-parser-output .side-box-text{flex:1;min-width:0}}@media(min-width:720px){.mw-parser-output .side-box{width:238px}.mw-parser-output .side-box-right{clear:right;float:right;margin-left:1em}.mw-parser-output .side-box-left{margin-right:1em}}</style><style data-mw-deduplicate="TemplateStyles:r1237033735">@media print{body.ns-0 .mw-parser-output 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srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/99/Wiktionary-logo-en-v2.svg/60px-Wiktionary-logo-en-v2.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/99/Wiktionary-logo-en-v2.svg/80px-Wiktionary-logo-en-v2.svg.png 2x" data-file-width="512" data-file-height="512" /></span></span></div> <div class="side-box-text plainlist">Look up <i><b><a href="https://en.wiktionary.org/wiki/adjuvant" class="extiw" title="wiktionary:adjuvant">adjuvant</a></b></i> in Wiktionary, the free dictionary.</div></div> </div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1235681985"><div class="side-box metadata side-box-right"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"> <div class="side-box-flex"> <div class="side-box-image"><span class="noviewer" typeof="mw:File"><span><img alt="" src="//upload.wikimedia.org/wikipedia/commons/thumb/3/32/Scholia_logo.svg/40px-Scholia_logo.svg.png" decoding="async" width="40" height="39" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/32/Scholia_logo.svg/60px-Scholia_logo.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/32/Scholia_logo.svg/80px-Scholia_logo.svg.png 2x" data-file-width="107" data-file-height="104" /></span></span></div> <div class="side-box-text plainlist"><a href="https://www.wikidata.org/wiki/Wikidata:Scholia" class="extiw" title="d:Wikidata:Scholia">Scholia</a> has a profile for <a href="https://iw.toolforge.org/scholia/Q967453" class="extiw" title="toolforge:scholia/Q967453"><b>immunologic adjuvant <small>(Q967453)</small></b></a>.</div></div> </div> <ul><li><a rel="nofollow" class="external text" href="http://www.mayoclinic.com/health/adjuvant-therapy/CA00012">Adjuvant therapy</a></li> <li><a rel="nofollow" class="external text" href="http://research.uiowa.edu/animal/?get=adjuvant">Animal research</a> <a rel="nofollow" class="external text" href="https://web.archive.org/web/20120227081855/http://research.uiowa.edu/animal/?get=adjuvant">Archived</a> 2012-02-27 at the <a href="/wiki/Wayback_Machine" title="Wayback Machine">Wayback Machine</a></li> <li><a rel="nofollow" class="external text" href="http://www.violinet.org/vaxjo">Vaxjo database</a> <a rel="nofollow" class="external text" href="https://web.archive.org/web/20200514012615/http://www.violinet.org/vaxjo">Archived</a> 2020-05-14 at the <a href="/wiki/Wayback_Machine" title="Wayback Machine">Wayback Machine</a></li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output 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navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Vaccines" title="Template:Vaccines"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Vaccines" title="Template talk:Vaccines"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Vaccines" title="Special:EditPage/Template:Vaccines"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Artificial_induction_of_immunity_/_Immunization:_Vaccines,_Vaccination,_Infection,_Inoculation_(J07)" style="font-size:114%;margin:0 4em"><a href="/wiki/Artificial_induction_of_immunity" title="Artificial induction of immunity">Artificial induction of immunity</a> / <a href="/wiki/Immunization" title="Immunization">Immunization</a>: <a href="/wiki/Vaccine" title="Vaccine">Vaccines</a>, <a href="/wiki/Vaccination" title="Vaccination">Vaccination</a>, <a href="/wiki/Infection" title="Infection">Infection</a>, <a href="/wiki/Inoculation" title="Inoculation">Inoculation</a> (<a href="/wiki/ATC_code_J07" title="ATC code J07">J07</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Development</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a class="mw-selflink selflink">Adjuvants</a></li> <li><a href="/wiki/Vaccine_ingredients" title="Vaccine ingredients">Vaccine ingredients</a> <ul><li><a href="/wiki/List_of_vaccine_excipients" title="List of vaccine excipients">list</a></li></ul></li> <li><a href="/wiki/Mathematical_modelling_of_infectious_diseases" title="Mathematical modelling of infectious diseases">Mathematical modelling</a></li> <li><a href="/wiki/Vaccine_storage" title="Vaccine storage">Storage</a></li> <li><a href="/wiki/Timeline_of_human_vaccines" title="Timeline of human vaccines">Timeline</a></li> <li><a href="/wiki/Vaccine_trial" title="Vaccine trial">Trials</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Classes</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Conjugate_vaccine" title="Conjugate vaccine">Conjugate</a></li> <li><a href="/wiki/Inactivated_vaccine" title="Inactivated vaccine">Inactivated</a></li> <li>Live <ul><li><a href="/wiki/Attenuated_vaccine" title="Attenuated vaccine">Attenuated</a></li> <li><a href="/wiki/Heterologous_vaccine" title="Heterologous vaccine">Heterologous</a></li></ul></li> <li><a href="/wiki/Subunit_vaccine" title="Subunit vaccine">Subunit/component</a> / <a href="/wiki/Peptide_vaccine" title="Peptide vaccine">Peptide</a> / <a href="/wiki/Virus-like_particle" title="Virus-like particle">Virus-like particle</a> / <a href="/wiki/Synthetic_vaccine" title="Synthetic vaccine">Synthetic</a></li> <li><a href="/wiki/DNA_vaccine" title="DNA vaccine">DNA</a> / <a href="/wiki/MRNA_vaccine" title="MRNA vaccine">mRNA</a></li> <li><a href="/wiki/Therapeutic_vaccines" title="Therapeutic vaccines">Therapeutic</a></li> <li><a href="/wiki/Toxoid" title="Toxoid">Toxoid</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Administration</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Global: <ul><li><a href="/wiki/GAVI" title="GAVI">GAVI Alliance</a></li> <li><a href="/wiki/National_Immunization_Technical_Advisory_Group" title="National Immunization Technical Advisory Group">NITAG</a></li> <li><a href="/wiki/Strategic_Advisory_Group_of_Experts" title="Strategic Advisory Group of Experts">SAGE</a></li> <li><a href="/wiki/Vaccine_wastage" title="Vaccine wastage">Vaccine wastage</a></li> <li><a href="/wiki/Vaccination_policy" title="Vaccination policy">Policy</a></li> <li><a href="/wiki/Vaccination_schedule" title="Vaccination schedule">Schedule</a></li> <li><a href="/wiki/Vaccine_adverse_event" title="Vaccine adverse event">Vaccine injury</a></li></ul></li> <li>US: <ul><li><a href="/wiki/Advisory_Committee_on_Immunization_Practices" title="Advisory Committee on Immunization Practices">ACIP</a></li> <li><a href="/wiki/National_Vaccine_Injury_Compensation_Program" title="National Vaccine Injury Compensation Program">Vaccine court</a></li> <li><a href="/wiki/Vaccines_for_Children_Program" title="Vaccines for Children Program">Vaccines for Children Program</a></li> <li><a href="/wiki/Vaccine_Adverse_Event_Reporting_System" title="Vaccine Adverse Event Reporting System">VAERS</a></li> <li><a href="/wiki/Vaccine_Safety_Datalink" title="Vaccine Safety Datalink">VSD</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Vaccines</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Bacterial</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anthrax_vaccine" title="Anthrax vaccine">Anthrax</a></li> <li><a href="/wiki/Brucellosis_vaccine" title="Brucellosis vaccine">Brucellosis</a></li> <li><a href="/wiki/Cholera_vaccine" title="Cholera vaccine">Cholera</a><sup>#</sup></li> <li><a href="/wiki/Diphtheria_vaccine" title="Diphtheria vaccine">Diphtheria</a><sup>#</sup></li> <li><a href="/wiki/Hib_vaccine" title="Hib vaccine">Hib</a><sup>#</sup></li> <li><a href="/wiki/Leptospirosis#Prevention" title="Leptospirosis">Leptospirosis</a></li> <li><a href="/wiki/Lyme_disease#Vaccination" title="Lyme disease">Lyme disease</a><sup>‡</sup></li> <li><a href="/wiki/Meningococcal_vaccine" title="Meningococcal vaccine">Meningococcus</a><sup>#</sup> <ul><li><a href="/wiki/MeNZB" title="MeNZB">MeNZB</a></li> <li><a href="/wiki/NmVac4-A/C/Y/W-135" title="NmVac4-A/C/Y/W-135">NmVac4-A/C/Y/W-135</a></li></ul></li> <li><a href="/wiki/Pertussis_vaccine" title="Pertussis vaccine">Pertussis</a><sup>#</sup></li> <li><a href="/wiki/Plague_vaccine" title="Plague vaccine">Plague</a></li> <li><a href="/wiki/Pneumococcal_vaccine" title="Pneumococcal vaccine">Pneumococcal</a><sup>#</sup> <ul><li><a href="/wiki/Pneumococcal_conjugate_vaccine" title="Pneumococcal conjugate vaccine">PCV</a></li> <li><a href="/wiki/Pneumococcal_polysaccharide_vaccine" title="Pneumococcal polysaccharide vaccine">PPSV</a></li></ul></li> <li><a href="/wiki/Q_fever#Prevention" title="Q fever">Q fever</a></li> <li><a href="/wiki/Tetanus_vaccine" title="Tetanus vaccine">Tetanus</a><sup>#</sup></li> <li><a href="/wiki/Tuberculosis_vaccines" title="Tuberculosis vaccines">Tuberculosis</a> <ul><li><a href="/wiki/BCG_vaccine" title="BCG vaccine">BCG</a><sup>#</sup></li></ul></li> <li><a href="/wiki/Typhoid_vaccine" title="Typhoid vaccine">Typhoid</a><sup>#</sup> <ul><li><a href="/wiki/Ty21a" title="Ty21a">Ty21a</a></li> <li><a href="/wiki/Vi_capsular_polysaccharide_vaccine" title="Vi capsular polysaccharide vaccine">ViCPS</a></li></ul></li> <li><a href="/wiki/Typhus_vaccine" title="Typhus vaccine">Typhus</a></li> <li>combination: <ul><li><a href="/wiki/DPT_vaccine" title="DPT vaccine">DPT/DTwP/DTaP</a></li> <li><a href="/wiki/Tetanus_vaccine" title="Tetanus vaccine">Td/Tdap</a></li></ul></li> <li>research: <ul><li><a href="/wiki/Clostridioides_difficile_infection#Research" title="Clostridioides difficile infection">Clostridioides difficile</a></li> <li><a href="/wiki/Group_B_streptococcal_infection#Vaccine" title="Group B streptococcal infection">Group B streptococcal disease</a></li> <li><a href="/wiki/Shigellosis#Vaccine" title="Shigellosis">Shigellosis</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Viral</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adenovirus_vaccine" title="Adenovirus vaccine">Adenovirus</a></li> <li><a href="/wiki/Chikungunya_vaccine" title="Chikungunya vaccine">Chikungunya</a></li> <li><a href="/wiki/Ebola_vaccine" title="Ebola vaccine">Ebola</a> <ul><li><a href="/wiki/RVSV-ZEBOV_vaccine" title="RVSV-ZEBOV vaccine">rVSV-ZEBOV</a></li></ul></li> <li><a href="/wiki/Influenza_vaccine" title="Influenza vaccine">Flu</a><sup>#</sup> <ul><li><a href="/wiki/2009_swine_flu_pandemic_vaccine" title="2009 swine flu pandemic vaccine">H1N1</a> (<a href="/wiki/Pandemrix" title="Pandemrix">Pandemrix</a>)</li> <li><a href="/wiki/H5N1_vaccine" title="H5N1 vaccine">H5N1</a></li> <li><a href="/wiki/H5N8_vaccine" title="H5N8 vaccine">H5N8</a></li> <li><a href="/wiki/Live_attenuated_influenza_vaccine" title="Live attenuated influenza vaccine">LAIV</a></li></ul></li> <li><a href="/wiki/Hantavirus_vaccine" title="Hantavirus vaccine">Hantavirus</a></li> <li><a href="/wiki/Hepatitis_A_vaccine" title="Hepatitis A vaccine">Hepatitis A</a><sup>#</sup></li> <li><a href="/wiki/Hepatitis_B_vaccine" title="Hepatitis B vaccine">Hepatitis B</a><sup>#</sup></li> <li><a href="/wiki/Hepatitis_E#Vaccines" title="Hepatitis E">Hepatitis E</a></li> <li><a href="/wiki/HPV_vaccine" title="HPV vaccine">HPV</a><sup>#</sup> <ul><li><a href="/wiki/Cervarix" title="Cervarix">Cervarix</a></li> <li><a href="/wiki/Gardasil" title="Gardasil">Gardasil</a></li></ul></li> <li><a href="/wiki/Japanese_encephalitis_vaccine" title="Japanese encephalitis vaccine">Japanese encephalitis</a><sup>#</sup></li> <li><a href="/wiki/Measles_vaccine" title="Measles vaccine">Measles</a><sup>#</sup></li> <li><a href="/wiki/Mpox_vaccine" class="mw-redirect" title="Mpox vaccine">Mpox</a></li> <li><a href="/wiki/Mumps_vaccine" title="Mumps vaccine">Mumps</a><sup>#</sup></li> <li><a href="/wiki/Polio_vaccine" title="Polio vaccine">Polio</a><sup>#</sup> <ul><li><a href="/wiki/Polio_vaccine#Attenuated" title="Polio vaccine">Sabin</a></li> <li><a href="/wiki/Polio_vaccine#Inactivated" title="Polio vaccine">Salk</a></li></ul></li> <li><a href="/wiki/Rabies_vaccine" title="Rabies vaccine">Rabies</a><sup>#</sup></li> <li><a href="/wiki/Rotavirus_vaccine" title="Rotavirus vaccine">Rotavirus</a><sup>#</sup></li> <li><a href="/wiki/Rubella_vaccine" title="Rubella vaccine">Rubella</a><sup>#</sup></li> <li><a href="/wiki/COVID-19_vaccine" title="COVID-19 vaccine">SARS-CoV-2</a> <ul><li><a href="/wiki/Corbevax" title="Corbevax">Corbevax</a><sup>†</sup></li> <li><a href="/wiki/Covaxin" title="Covaxin">Bharat Biotech</a><sup>†</sup></li> <li><a href="/wiki/Convidecia" title="Convidecia">CanSino</a><sup>†</sup></li> <li><a href="/wiki/CoronaVac" title="CoronaVac">CoronaVac</a><sup>†</sup></li> <li><a href="/wiki/EpiVacCorona" title="EpiVacCorona">EpiVacCorona</a><sup>†</sup></li> <li><a href="/wiki/Janssen_COVID-19_vaccine" title="Janssen COVID-19 vaccine">Janssen</a></li> <li><a href="/wiki/Moderna_COVID-19_vaccine" title="Moderna COVID-19 vaccine">Moderna</a></li> <li><a href="/wiki/Novavax_COVID-19_vaccine" title="Novavax COVID-19 vaccine">Novavax</a></li> <li><a href="/wiki/Oxford%E2%80%93AstraZeneca_COVID-19_vaccine" title="Oxford–AstraZeneca COVID-19 vaccine">Oxford–AstraZeneca</a></li> <li><a href="/wiki/Pfizer%E2%80%93BioNTech_COVID-19_vaccine" title="Pfizer–BioNTech COVID-19 vaccine">Pfizer–BioNTech</a></li> <li><a href="/wiki/Sanofi%E2%80%93GSK_COVID-19_vaccine" title="Sanofi–GSK COVID-19 vaccine">Sanofi–GSK</a><sup>†</sup></li> <li><a href="/wiki/Sinopharm_BIBP_COVID-19_vaccine" title="Sinopharm BIBP COVID-19 vaccine">Sinopharm BIBP</a><sup>†</sup></li> <li><a href="/wiki/Skycovione" title="Skycovione">Skycovione</a><sup>†</sup></li> <li><a href="/wiki/Sputnik_V_COVID-19_vaccine" title="Sputnik V COVID-19 vaccine">Sputnik V</a><sup>†</sup></li> <li><a href="/wiki/Valneva_COVID-19_vaccine" title="Valneva COVID-19 vaccine">Valneva</a><sup>†</sup></li></ul></li> <li><a href="/wiki/Respiratory_syncytial_virus_vaccine" title="Respiratory syncytial virus vaccine">Respiratory syncytial virus (RSV)</a></li> <li><a href="/wiki/Smallpox_vaccine" title="Smallpox vaccine">Smallpox</a></li> <li><a href="/wiki/Tick-borne_encephalitis_vaccine" title="Tick-borne encephalitis vaccine">Tick-borne encephalitis</a><sup>#</sup></li> <li>Varicella zoster <ul><li><a href="/wiki/Varicella_vaccine" title="Varicella vaccine">Chicken pox</a><sup>#</sup></li> <li><a href="/wiki/Zoster_vaccine" title="Zoster vaccine">Shingles</a></li></ul></li> <li><a href="/wiki/Yellow_fever_vaccine" title="Yellow fever vaccine">Yellow fever</a><sup>#</sup></li> <li>combination: <ul><li><a href="/wiki/Hepatitis_A_and_B_vaccine" title="Hepatitis A and B vaccine">Hepatitis A and B</a></li> <li><a href="/wiki/MMR_vaccine" title="MMR vaccine">MMR</a></li> <li><a href="/wiki/MMRV_vaccine" title="MMRV vaccine">MMRV</a></li></ul></li> <li>research: <ul><li><a href="/wiki/Cytomegalovirus_vaccine" title="Cytomegalovirus vaccine">Cytomegalovirus</a></li> <li><a href="/wiki/Dengue_vaccine" title="Dengue vaccine">Dengue</a><sup>#</sup></li> <li><a href="/wiki/Epstein%E2%80%93Barr_virus_vaccine" title="Epstein–Barr virus vaccine">Epstein–Barr virus</a></li> <li><a href="/wiki/Hepatitis_C_vaccine" title="Hepatitis C vaccine">Hepatitis C</a></li> <li><a href="/wiki/Herpes_simplex_research" title="Herpes simplex research">Herpes simplex</a></li> <li><a href="/wiki/HIV_vaccine_development" title="HIV vaccine development">HIV</a></li> <li><a href="/wiki/Zika_virus_vaccine" title="Zika virus vaccine">Zika</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Protozoan</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Malaria_vaccine" title="Malaria vaccine">Malaria</a> <ul><li><a href="/wiki/RTS,S" title="RTS,S">RTS,S</a></li></ul></li> <li>research: <ul><li><a href="/wiki/Trypanosomiasis_vaccine" title="Trypanosomiasis vaccine">Trypanosomiasis</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Helminthiasis" title="Helminthiasis">Helminthiasis</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>research: <ul><li><a href="/wiki/Hookworm_vaccine" title="Hookworm vaccine">Hookworm</a></li> <li><a href="/wiki/Schistosomiasis_vaccine" title="Schistosomiasis vaccine">Schistosomiasis</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Androvax" title="Androvax">Androvax (androstenedione albumin)</a></li> <li><a href="/wiki/Cancer_vaccine" title="Cancer vaccine">Cancer vaccines</a> <ul><li><a href="/wiki/ALVAC-CEA_vaccine" title="ALVAC-CEA vaccine">ALVAC-CEA</a></li> <li><a href="/wiki/BCG_vaccine" title="BCG vaccine">BCG</a><sup>#</sup></li> <li><a href="/wiki/Hepatitis_B_vaccine" title="Hepatitis B vaccine">Hepatitis B</a><sup>#</sup></li> <li><a href="/wiki/HPV_vaccine" title="HPV vaccine">HPV</a><sup>#</sup> <ul><li><a href="/wiki/Cervarix" title="Cervarix">Cervarix</a></li> <li><a href="/wiki/Gardasil" title="Gardasil">Gardasil</a></li></ul></li> <li><a href="/wiki/Prostvac" title="Prostvac">Prostvac</a></li></ul></li> <li><a href="/wiki/NicVAX" title="NicVAX">NicVAX</a></li> <li><a href="/wiki/Ovandrotone_albumin" title="Ovandrotone albumin">Ovandrotone albumin (Fecundin)</a></li> <li><a href="/wiki/TA-CD" title="TA-CD">TA-CD</a></li> <li><a href="/wiki/TA-NIC" title="TA-NIC">TA-NIC</a></li> <li>combination: <ul><li><a href="/wiki/DTaP-IPV/Hib_vaccine" title="DTaP-IPV/Hib vaccine">DTaP-IPV/Hib</a></li> <li><a href="/wiki/DTaP-IPV-HepB_vaccine" title="DTaP-IPV-HepB vaccine">DTaP-IPV-HepB</a></li> <li><a href="/wiki/DTwP-HepB-Hib_vaccine" title="DTwP-HepB-Hib vaccine">DTwP-HepB-Hib</a></li> <li><a href="/wiki/Hexavalent_vaccine" title="Hexavalent vaccine">Hexavalent vaccine</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Inventors/<br />researchers</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Edward_Jenner" title="Edward Jenner">Edward Jenner</a></li> <li><a href="/wiki/Louis_Pasteur" title="Louis Pasteur">Louis Pasteur</a></li> <li><a href="/wiki/Hilary_Koprowski" title="Hilary Koprowski">Hilary Koprowski</a></li> <li><a href="/wiki/Jonas_Salk" title="Jonas Salk">Jonas Salk</a></li> <li><a href="/wiki/John_Franklin_Enders" title="John Franklin Enders">John Franklin Enders</a></li> <li><a href="/wiki/Maurice_Hilleman" title="Maurice Hilleman">Maurice Hilleman</a></li> <li><a href="/wiki/Stanley_Plotkin" title="Stanley Plotkin">Stanley Plotkin</a></li> <li><a href="/wiki/H._Fred_Clark" title="H. Fred Clark">H. Fred Clark</a></li> <li><a href="/wiki/Paul_Offit" title="Paul Offit">Paul Offit</a></li> <li><a href="/wiki/Katalin_Karik%C3%B3" title="Katalin Karikó">Katalin Karikó</a></li> <li><a href="/wiki/Drew_Weissman" title="Drew Weissman">Drew Weissman</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Controversy</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Vaccine_hesitancy" title="Vaccine hesitancy">General</a></li> <li><a href="/wiki/MMR_vaccine_and_autism" title="MMR vaccine and autism">MMR</a> (<a href="/wiki/Lancet_MMR_autism_fraud" title="Lancet MMR autism fraud"><i>Lancet</i> MMR autism fraud</a>)</li> <li><a href="/wiki/National_Childhood_Vaccine_Injury_Act" title="National Childhood Vaccine Injury Act">NCVIA</a></li> <li><a href="/wiki/Pox_party" title="Pox party">Pox party</a></li> <li><a href="/wiki/Thiomersal_and_vaccines" title="Thiomersal and vaccines">Thiomersal</a></li> <li><a href="/wiki/Vaccines_and_SIDS" title="Vaccines and SIDS">Vaccines and SIDS</a></li> <li><i><a href="/wiki/Cedillo_v._Secretary_of_Health_and_Human_Services" title="Cedillo v. Secretary of Health and Human Services">Cedillo v. Secretary of Health and Human Services</a></i></li> <li><a href="/wiki/Alternative_vaccination_schedule" title="Alternative vaccination schedule">Alternative vaccination schedule</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Related</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Epidemiology" title="Epidemiology">Epidemiology</a></li> <li><a href="/wiki/Eradication_of_infectious_diseases" title="Eradication of infectious diseases">Eradication of infectious diseases</a></li> <li><a href="/wiki/Vaccinate_Your_Family" title="Vaccinate Your Family">Vaccinate Your Family</a></li> <li><a href="/wiki/List_of_vaccine_topics" title="List of vaccine topics">List of vaccine topics</a></li></ul> </div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="background: transparent; padding: 0px;"><div><div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table></div>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Immunologic_adjuvant&oldid=1243784817">https://en.wikipedia.org/w/index.php?title=Immunologic_adjuvant&oldid=1243784817</a>"</div></div> <div id="catlinks" class="catlinks" data-mw="interface"><div id="mw-normal-catlinks" class="mw-normal-catlinks"><a href="/wiki/Help:Category" title="Help:Category">Categories</a>: <ul><li><a href="/wiki/Category:Adjuvants" title="Category:Adjuvants">Adjuvants</a></li><li><a href="/wiki/Category:Immunology" title="Category:Immunology">Immunology</a></li></ul></div><div id="mw-hidden-catlinks" class="mw-hidden-catlinks mw-hidden-cats-hidden">Hidden categories: <ul><li><a href="/wiki/Category:Webarchive_template_wayback_links" title="Category:Webarchive template wayback links">Webarchive template wayback links</a></li><li><a href="/wiki/Category:Articles_with_short_description" title="Category:Articles with short description">Articles with short description</a></li><li><a href="/wiki/Category:Short_description_is_different_from_Wikidata" title="Category:Short description is different from Wikidata">Short description is different from Wikidata</a></li><li><a href="/wiki/Category:Articles_containing_Latin-language_text" title="Category:Articles containing Latin-language text">Articles containing Latin-language text</a></li><li><a href="/wiki/Category:All_articles_with_unsourced_statements" title="Category:All articles with unsourced statements">All articles with unsourced statements</a></li><li><a href="/wiki/Category:Articles_with_unsourced_statements_from_February_2021" title="Category:Articles with unsourced statements from February 2021">Articles with unsourced statements from February 2021</a></li><li><a href="/wiki/Category:Articles_containing_potentially_dated_statements_from_2006" title="Category:Articles containing potentially dated statements from 2006">Articles containing potentially dated statements from 2006</a></li><li><a href="/wiki/Category:All_articles_containing_potentially_dated_statements" title="Category:All articles containing potentially dated statements">All articles containing potentially dated statements</a></li></ul></div></div> </div> </main> </div> <div class="mw-footer-container"> <footer id="footer" class="mw-footer" > <ul id="footer-info"> <li id="footer-info-lastmod"> This page was last edited on 3 September 2024, at 12:27<span class="anonymous-show"> (UTC)</span>.</li> <li id="footer-info-copyright">Text is available under the <a href="/wiki/Wikipedia:Text_of_the_Creative_Commons_Attribution-ShareAlike_4.0_International_License" title="Wikipedia:Text of the Creative Commons Attribution-ShareAlike 4.0 International License">Creative Commons Attribution-ShareAlike 4.0 License</a>; additional terms may apply. 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