{{Short description|Combination of adjuvants}} '''Adjuvant System 04''' or '''AS04''' is a trade name for a combination of adjuvants used in various vaccine products by GlaxoSmithKline,<ref>{{cite web |archive-url=https://web.archive.org/web/20090105155919/http://www.gsk.com./media/flu/flu-adjuvant.pdf |title=Vaccine Adjuvant System Technology Background Information |archive-date=2009-01-05 |url=http://www.gsk.com./media/flu/flu-adjuvant.pdf }}</ref> in particular the Fendrix<ref>{{cite web |archive-url=https://web.archive.org/web/20130304100126/http://hcp.gsk.co.uk/products/fendrix.html |archive-date=2013-03-04 |url=http://hcp.gsk.co.uk/products/fendrix.html |title=Products | GSKpro }}</ref> hepatitis B vaccine and Cervarix<ref>{{cite web |archive-url=https://web.archive.org/web/20090529055125/http://cervarix.co.uk/adjuvants_as04.asp |archive-date=2009-05-29 |url=http://cervarix.co.uk/adjuvants_as04.asp |title=Products | GSKpro }}</ref> human papillomavirus (HPV) vaccine. It consists of aluminium hydroxide and monophosphoryl lipid A (MPL). It is the successor of AS03, a squalene based adjuvant used in H1N1/09 and H5N1 influenza vaccines.<ref>{{Cite book|chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9781455700905000136 |doi=10.1016/B978-1-4557-0090-5.00013-6 |chapter=Technologies for making new vaccines |title=Vaccines |year=2013 |last1=Ellis |first1=Ronald W. |last2=Rappuoli |first2=Rino |last3=Ahmed |first3=Sohail |pages=1182–1199 |isbn=9781455700905 |edition=Sixth |editor-first1=Stanley A. |editor-last1=Plotkin |editor-first2=Walter A. |editor-last2=Orenstein |editor-first3=Paul A. |editor-last3=Offit |publisher=W.B. Saunders}}</ref><ref>{{Cite book| chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780120884032500113 | doi=10.1016/B978-012088403-2/50011-3 | chapter=Development and evaluation of AS04, a novel and improved adjuvant system containing MPL and aluminum salt | title=Immunopotentiators in Modern Vaccines | year=2006 | last1=Garçon | first1=Nathalie | last2=Van Mechelen | first2=Marcelle | last3=Wettendorff | first3=Martine | pages=161–177 | isbn=9780120884032 }}</ref><ref>{{Cite journal| doi=10.1016/j.vaccine.2019.07.098 | title=Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood | year=2019 | last1=Laupèze | first1=Béatrice | last2=Hervé | first2=Caroline | last3=Di Pasquale | first3=Alberta | last4=Tavares Da Silva | first4=Fernanda | journal=Vaccine | volume=37 | issue=38 | pages=5670–5680 | pmid=31420171 | s2cid=201042219 | doi-access=free }}</ref><ref>{{Cite journal|pmc=5287309 |year=2016 |last1=Garçon |first1=N. |last2=Di Pasquale |first2=A. |title=From discovery to licensure, the Adjuvant System story |journal=Human Vaccines & Immunotherapeutics |volume=13 |issue=1 |pages=19–33 |doi=10.1080/21645515.2016.1225635 |pmid=27636098 }}</ref>
== Efficacy and safety == === HPV vaccines === Studies on an AS04-adjuvanted HPV-16/18 vaccine showed a high and sustained immune response to HPV antigens after injection, including in patients receiving subsequent doses.<ref>{{Cite journal|pmid=21815697 |year=2011 |last1=Garçon |first1=N. |last2=Morel |first2=S. |last3=Didierlaurent |first3=A. |last4=Descamps |first4=D. |last5=Wettendorff |first5=M. |last6=Van Mechelen |first6=M. |title=Development of an AS04-adjuvanted HPV vaccine with the adjuvant system approach |journal=BioDrugs |volume=25 |issue=4 |pages=217–226 |doi=10.2165/11591760-000000000-00000 |s2cid=25608550 |doi-access=free }}</ref><ref>{{Cite journal|url=https://link.springer.com/article/10.2165/00003495-200868030-00007 |doi=10.2165/00003495-200868030-00007 |title=Human Papillomavirus Types 16 and 18 Vaccine (Recombinant, AS04 Adjuvanted, Adsorbed (Cervarix)) |year=2008 |last1=Keam |first1=Susan J. |last2=Harper |first2=Diane M. |journal=Drugs |volume=68 |issue=3 |pages=359–372 |pmid=18257611 |s2cid=39629514 |url-access=subscription }}</ref><ref>{{Cite journal|url=https://www.sciencedirect.com/science/article/abs/pii/S0264410X08015004 |doi=10.1016/j.vaccine.2008.10.088 |title=Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15–55 years |year=2009 |last1=Schwarz |first1=Tino F. |last2=Spaczynski |first2=Marek |last3=Schneider |first3=Achim |last4=Wysocki |first4=Jacek |last5=Galaj |first5=Andrzej |last6=Perona |first6=Pamela |last7=Poncelet |first7=Sylviane |last8=Zahaf |first8=Toufik |last9=Hardt |first9=Karin |last10=Descamps |first10=Dominique |last11=Dubin |first11=Gary |author12=HPV Study Group for Adult Women |journal=Vaccine |volume=27 |issue=4 |pages=581–587 |pmid=19022320 |url-access=subscription }}</ref> Immune response was enhanced by the MPL component which triggered local NF-kB and cytokine production, leading to increased activation of antigen-presenting cells.<ref>{{Cite journal|last1=Didierlaurent|first1=Arnaud M.|last2=Morel|first2=Sandra|last3=Lockman|first3=Laurence|last4=Giannini|first4=Sandra L.|last5=Bisteau|first5=Michel|last6=Carlsen|first6=Harald|last7=Kielland|first7=Anders|last8=Vosters|first8=Olivier|last9=Vanderheyde|first9=Nathalie|last10=Schiavetti|first10=Francesca|last11=Larocque|first11=Daniel|date=2009-11-15|title=AS04, an Aluminum Salt- and TLR4 Agonist-Based Adjuvant System, Induces a Transient Localized Innate Immune Response Leading to Enhanced Adaptive Immunity|url=https://www.jimmunol.org/content/183/10/6186|journal=The Journal of Immunology|language=en|volume=183|issue=10|pages=6186–6197|doi=10.4049/jimmunol.0901474|issn=0022-1767|pmid=19864596|doi-access=free}}</ref> Immune response duration was extended by the aluminium hydroxide component. The HPV-16/18 AS04-adjuvanted vaccine showed enhanced efficacy compared to an aluminium salt-adjuvanted formulation, with a higher level of antibodies subsequently detected in the body.<ref>{{Cite journal|doi=10.1016/j.vaccine.2006.06.005 |title=Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/Aluminium salt combination (AS04) compared to aluminium salt only |year=2006 |last1=Giannini |first1=S. |last2=Hanon |first2=E. |last3=Moris |first3=P. |last4=Vanmechelen |first4=M. |last5=Morel |first5=S. |last6=Dessy |first6=F. |last7=Fourneau |first7=M. |last8=Colau |first8=B. |last9=Suzich |first9=J. |last10=Losonksy |first10=G. |last11=Martin |first11=M. T. |last12=Dubin |first12=G. |last13=Wettendorff |first13=M. A. |journal=Vaccine |volume=24 |issue=33–34 |pages=5937–5949 |pmid=16828940 |doi-access=free }}</ref>
Long-term studies appear to show an adequate efficacy and safety profile.<ref>{{Cite journal|doi=10.1080/21645515.2019.1692557 |title=Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12–15 years: End-of-study results from a community-randomized study up to 6.5 years |year=2020 |last1=Bi |first1=Dan |last2=Apter |first2=Dan |last3=Eriksson |first3=Tiina |last4=Hokkanen |first4=Mari |last5=Zima |first5=Julia |last6=Damaso |first6=Silvia |last7=Soila |first7=Maaria |last8=Dubin |first8=Gary |last9=Lehtinen |first9=Matti |last10=Struyf |first10=Frank |journal=Human Vaccines & Immunotherapeutics |volume=16 |issue=6 |pages=1392–1403 |pmid=31829767 |pmc=7482795 |s2cid=209341449 }}</ref><ref>{{Cite journal|doi=10.1016/S0140-6736(09)61567-1 |title=Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: Analysis of a randomised placebo-controlled trial up to 6·4 years |journal=The Lancet |year=2009 |volume=374 |issue=9706 |pages=1975–1985 |pmid=19962185 |author1=GlaxoSmithKline Vaccine HPV-007 Study Group |last2=Romanowski |first2=B. |last3=De Borba |first3=P. C. |last4=Naud |first4=P. S. |last5=Roteli-Martins |first5=C. M. |last6=De Carvalho |first6=N. S. |last7=Teixeira |first7=J. C. |last8=Aoki |first8=F. |last9=Ramjattan |first9=B. |last10=Shier |first10=R. M. |last11=Somani |first11=R. |last12=Barbier |first12=S. |last13=Blatter |first13=M. M. |last14=Chambers |first14=C. |last15=Ferris |first15=D. |last16=Gall |first16=S. A. |last17=Guerra |first17=F. A. |last18=Harper |first18=D. M. |last19=Hedrick |first19=J. A. |last20=Henry |first20=D. C. |last21=Korn |first21=A. P. |last22=Kroll |first22=R. |last23=Moscicki |first23=A. B. |last24=Rosenfeld |first24=W. D. |last25=Sullivan |first25=B. J. |last26=Thoming |first26=C. S. |last27=Tyring |first27=S. K. |last28=Wheeler |first28=C. M. |last29=Dubin |first29=G. |last30=Schuind |first30=A. |s2cid=30776042 |display-authors=1 }}</ref>
=== Hepatitis B vaccines === AS04-adjuvanted HBV vaccines may be relevant for patients that are non-responsive to other HBV vaccines,<ref>{{Cite journal|doi=10.3390/vaccines9030279 |doi-access=free |title=Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination |year=2021 |last1=Tejada-Pérez |first1=Juan José |last2=Vázquez-Vicente |first2=Juan José |last3=Herrera-Burgos |first3=María Renée |last4=Martín-Martín |first4=Francisco Gabriel |last5=Parrón-Carreño |first5=Tesifón |last6=Alarcón-Rodríguez |first6=Raquel |journal=Vaccines |volume=9 |issue=3 |page=279 |pmid=33808589 |pmc=8003400 }}</ref> including those with immunodeficiency.<ref>{{Cite journal|doi=10.1097/QAD.0000000000002085 |title=Vaccination with Fendrix of prior nonresponding patients with HIV has a high success rate |year=2019 |last1=Machiels |first1=Julian D. |last2=Braam |first2=Esmée E. |last3=Van Bentum |first3=Petra |last4=Van Vugt |first4=Michèle |last5=De Vries-Sluijs |first5=Theodora E.M.S. |last6=Schouten |first6=Ineke W.E.M. |last7=Bierman |first7=Wouter F.W. |last8=Gisolf |first8=Elisabeth H. |journal=AIDS |volume=33 |issue=3 |pages=503–507 |pmid=30702518 |s2cid=73414009 |doi-access=free |hdl=1765/119465 |hdl-access=free }}</ref><ref>{{Cite journal|pmc=9416157 |year=2022 |last1=Horta |first1=D. |last2=Forné |first2=M. |last3=Agustí |first3=A. |last4=Raga |first4=A. |last5=Martín-Cardona |first5=A. |last6=Hernández-Soto |first6=J. M. |last7=Ruiz-Ramírez |first7=P. |last8=Esteve-Comas |first8=M. |title=Efficacy of Hepatitis B Virus Vaccines HBVaxpro40© and Fendrix© in Patients with Chronic Liver Disease in Clinical Practice |journal=Vaccines |volume=10 |issue=8 |page=1323 |doi=10.3390/vaccines10081323 |pmid=36016211 |doi-access=free }}</ref><ref>{{Cite journal|doi=10.1111/j.1523-1755.2005.00689.x |title=Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients |year=2005 |last1=Chiew Tong |first1=Norella Kong |last2=Beran |first2=Jiri |last3=Kee |first3=Swee Ann |last4=Miguel |first4=Jose Luisa |last5=Sannchez |first5=Carmen |last6=Bayas |first6=Jose Maria |last7=Vilella |first7=A. |last8=De Juanes |first8=J.R. |last9=Arrazola |first9=P. |last10=Calbo-Torrecillas |first10=Francisco |last11=De Novales |first11=Eduardo Lapez |last12=Hamtiaux |first12=Virginie |last13=Lievens |first13=Marc |last14=Stoffel |first14=Michel |journal=Kidney International |volume=68 |issue=5 |pages=2298–2303 |pmid=16221232 |s2cid=25535605 |doi-access=free }}</ref><ref>{{Cite journal|doi=10.1016/j.clinre.2019.06.010 |title=HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population |year=2020 |last1=Fabrizi |first1=Fabrizio |last2=Cerutti |first2=Roberta |last3=Nardelli |first3=Luca |last4=Tripodi |first4=Federica |last5=Messa |first5=Piergiorgio |journal=Clinics and Research in Hepatology and Gastroenterology |volume=44 |issue=1 |pages=49–56 |pmid=31327620 |hdl=2434/672871 |s2cid=198135022 |hdl-access=free }}</ref><ref>{{Cite journal|doi=10.1016/j.clinre.2020.01.010 |title=Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial |year=2020 |last1=Fabrizi |first1=Fabrizio |last2=Cerutti |first2=Roberta |last3=Garcia-Agudo |first3=Rebeca |last4=Bellincioni |first4=Cecilia |last5=Porata |first5=Giulia |last6=Frontini |first6=Giulia |last7=Aoufi-Rabih |first7=Sami |last8=Messa |first8=Piergiorgio |journal=Clinics and Research in Hepatology and Gastroenterology |volume=44 |issue=6 |pages=905–912 |pmid=32144074 |s2cid=212622741 }}</ref><ref>{{Cite journal|doi=10.1159/000368534 |title=Recombinant Hepatitis B Vaccine Adjuvanted with AS04 in Dialysis Patients: A Prospective Cohort Study |year=2015 |last1=Fabrizi |first1=Fabrizio |last2=Tarantino |first2=Antonio |last3=Castelnovo |first3=Claudia |last4=Martin |first4=Paul |last5=Messa |first5=Piergiorgio |journal=Kidney and Blood Pressure Research |volume=40 |issue=6 |pages=584–592 |pmid=26566033 |s2cid=207555753 |hdl=2434/588627 |hdl-access=free }}</ref>
==See also== *AS03 *HPV vaccine *Hepatitis B vaccine
==References== {{Reflist}}
Category:Adjuvants