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Comparative Study
. 2018 Jan 31;19(1):6.
doi: 10.1186/s12865-018-0245-0.

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

Sumera Y Younis  1 , Christophe Barnier-Quer  2 , Simon Heuking  2 , Vinod Sommandas  1 , Livia Brunner  2 , Nicole Vd Werff  1 , Patrice Dubois  2 , Martin Friede  3 , Clemens Kocken  1 , Nicolas Collin  2 , Ed Remarque  4
Affiliations
Comparative Study

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

Sumera Y Younis et al. BMC Immunol. .

Abstract

Background: 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. 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.

Results: The 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.

Conclusions: The 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.

Keywords: AMA1; Adjuvants; Ag85A; Aluminium oxyhydroxide; HBsAg; Hepatitis B; Plasmodium falciparum; QS21; Squalene-in-water SWE; Tuberculosis.

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Conflict of interest statement

Authors’ information

SYY, VS, NW, CK and ER are employees of Biomedical Primate Research Centre, The Netherlands. CB, SH, LB and NC are employees of the Vaccine Formulation Laboratory, University of Lausanne, Switzerland. PD is self-employed. MF is an employee of WHO, Switzerland.

Ethics approval

All animal work was performed under the guidelines of Biomedical Primate Research Centre (BPRC) which uses protocols conforming to European animal welfare regulations. The independent ethics committee at BPRC, constituted according to Dutch law on animal experiments, approved the study protocol (number DEC 658) prior to start of the experiment.

Consent for publication

Not Applicable.

Competing interests

Authors declare no competing financial interests. SYY, VS, NW, CK and ER are employees of Biomedical Primate Research Centre, The Netherlands. CB, SH, LB and NC are employees of the Vaccine Formulation Laboratory, University of Lausanne, Switzerland. PD is self-employed. MF is an employee of WHO, Switzerland.

Figures

Fig. 1
Fig. 1
IFN-γ spots per 106 spleen cells plotted for the three antigens with the three adjuvants. Boxes indicate quartile ranges (bottom and top) and medians (middle). Same symbol within each treatment group refers to the same animal throughout all graphs
Fig. 2
Fig. 2
IL-5 spots per 106 spleen cells plotted for the three antigens with the three adjuvants. Boxes indicate quartile ranges (bottom and top) and medians (middle). Same symbol within each treatment group refers to the same animal throughout all graphs
Fig. 3
Fig. 3
IgGt Median number of total IgG titres in AU/mL shown for the three antigens with the three adjuvants. Same symbol within each treatment group refers to the same animal throughout all graphs
Fig. 4
Fig. 4
IgG1 Median number of IgG1 titres in AU/mL shown for the three antigens with the three adjuvants. Same symbol within each treatment group refers to the same animal throughout all graphs
Fig. 5
Fig. 5
IgG2b Median number of IgG2b titres in AU/mL shown for the three antigens with the three adjuvants. Same symbol within each treatment group refers to the same animal throughout all graphs
Fig. 6
Fig. 6
IgG2c Median number of IgG2c titres in AU/mL shown for the three antigens with the three adjuvants. Same symbol within each treatment group refers to the same animal throughout all graphs
See this image and copyright information in PMC

References

    1. Kawano Y, Noma T, Yata J. Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2. J Immunol. 1994;153(11):4948–4958. - PubMed
    1. Purkerson JM, Isakson PC. Interleukin 5 (IL-5) provides a signal that is required in addition to IL-4 for isotype switching to immunoglobulin (Ig) G1 and IgE. J Exp Med. 1992;175(4):973–982. doi: 10.1084/jem.175.4.973. - DOI - PMC - PubMed
    1. Mizoguchi C, et al. IL-5 induces IgG1 isotype switch recombination in mouse CD38-activated sIgD-positive B lymphocytes. J Immunol. 1999;162(5):2812–2819. - PubMed
    1. Martin RM, Brady JL, Lew AM. The need for IgG2c specific antiserum when isotyping antibodies from C57BL/6 and NOD mice. J Immunol Methods. 1998;212(2):187–192. doi: 10.1016/S0022-1759(98)00015-5. - DOI - PubMed
    1. Jouvin-Marche E, et al. The mouse Igh-1a and Igh-1b H chain constant regions are derived from two distinct isotypic genes. Immunogenetics. 1989;29(2):92–97. doi: 10.1007/BF00395856. - DOI - PubMed

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