Preclinical Development of AS04
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.
Key wordsAS04 Adjuvant System MPL formulation immune response TLR-4 vaccine
The author is thankful to Ulrike Krause and Pascal Cadot for their assistance in the preparation of the chapter. FENDrix and Cervarix are trade marks of the GlaxoSmithKline group of companies.
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