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BMC Immunol ; 19(1): 6, 2018 01 31.
Article in English | MEDLINE | ID: mdl-29386070

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.


Subject(s)
Adjuvants, Immunologic/analysis , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunospot Assay/methods , Vaccines/analysis , Acyltransferases/immunology , Animals , Antigens, Bacterial/immunology , Antigens, Protozoan/immunology , Hepatitis B Surface Antigens/immunology , Immunization , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-5/immunology , Interleukin-5/metabolism , Membrane Proteins/immunology , Mice, Inbred C57BL , Protozoan Proteins/immunology , Reproducibility of Results , Spleen/cytology , Spleen/immunology , Spleen/metabolism , Vaccines/immunology
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