Preclinical development of AS04

Methods in Molecular Biology
Nathalie Garçon

Abstract

Recent knowledge on vaccine-induced immunity led to the development of vaccine Adjuvant Systems specially designed and adapted to vaccine needs. AS04 is such a tailored Adjuvant System developed by GlaxoSmithKline Biologicals. This chapter focuses on the methods that were used during the preclinical evaluation of AS04. AS04 consists of the combination of aluminum salts and 3(')-O-deacylated monophosphoryl lipid A (MPL), a detoxified lipid A derivative with retained immunostimulatory capa- city. MPL also induces considerably less pro-inflammatory cytokines, as compared to the parent LPS molecule. Preclinical evaluation of AS04 allowed the determination of the optimal size of MPL particles. The added value of MPL in AS04-based formulations was evidenced by higher vaccine-elicited antibody responses, as well as the induction of higher levels of memory B cells, as compared to aluminum alone formulations. Preclinical evaluation demonstrated the relevance of using AS04 in situations where high and long-lasting antibody levels are needed. This represents the basis for the successful application of AS04 in vaccines against hepatitis B virus and human papillomavirus.

Citations

Jan 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Brittany D NeedhamM Stephen Trent
Apr 29, 2015·Human Vaccines & Immunotherapeutics·Alicja E Grzegorzewska
Jul 1, 2016·Annual Review of Microbiology·Jeremy C HendersonM Stephen Trent
Jun 8, 2011·Immunology and Cell Biology·Michael de VeerEls N T Meeusen
Aug 26, 2014·Expert Review of Vaccines·Alicja E Grzegorzewska
Nov 7, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Antonio HernandezJulia K Bohannon
Feb 16, 2021·Emerging Microbes & Infections·Chun-Lan ZhuangNing-Shao Xia
Jul 28, 2021·Advanced Drug Delivery Reviews·Matilde Durán-LobatoMaría José Alonso

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