Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation

Sumera Y Younis,Christophe Barnier-Quer,Patrice Dubois,Simon Heuking,Nicole Vd.Werff,Livia Brunner,Ed Remarque,Vinod Sommandas,Clemens Kocken,Nicolas Collin,Martin Friede

doi:10.1186/s12865-018-0245-0

Abstract

BackgroundThe need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21.ResultsThe nine antigen/adjuvant formulations were assessed for stability and immunogenicity in mice in order to provide benchmarks against which other formulations could be compared, in order to assist subsequent down selection of adjuvanted vaccines. Furthermore, mouse cellular immune responses were analyzed by measuring IFN-γ and IL-5 production in splenocytes by ELISPOT, and humoral responses were determined by antigen-specific ELISA, where levels of total IgG, IgG1, IgG2b and IgG2c in serum samples were determined.ConclusionsThe reference antigens and adjuvants described in this study, which span a spectrum of immune responses, are of potential use as tools to act as points of reference in vaccine development studies. The harmonized methodology described herein may be used as a tool for adjuvant/antigen comparison studies.

Highlights

The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development
The findings described above have allowed the development of a harmonized protocol which may prove useful for the down selection of vaccine adjuvants during preclinical studies
The data presented here is the foundation of this harmonization, and compares the immune responses observed in mice using three adjuvants formulated with three model antigens

Summary

Introduction

The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. The development of harmonized assays, including harmonized reagents capable of providing benchmarking tools by which new adjuvants can be evaluated and down selected is of clear benefit. Such tools may prove to be useful for the comparison of formulations across studies performed at different times and places. In order to develop such tools we have defined and established a set of laboratory assays and reagents that can be used as a harmonized benchmarking tool.

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Conclusion