Evaluation of the safety and immunogenicity of Plasmodium falciparum apical membrane antigen 1, merozoite surface protein 1 or RTS,S vaccines with adjuvant system AS02A administered alone or concurrently in rhesus monkeys

• Published in: Vaccine 2009-12, Vol.28 (2), p.452-462
• Main Authors: Pichyangkul, S, Tongtawe, P, Kum-Arb, U, Yongvanitchit, K, Gettayacamin, M, Hollingdale, M.R, Limsalakpetch, A, Stewart, V.A, Lanar, D.E, Dutta, S, Angov, E, Ware, L.A, Bergmann-Leitner, E.S, House, B, Voss, G, Dubois, M.C, Cohen, J.D, Fukuda, M.M, Heppner, D.G, Miller, R.S
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antigens, Protozoan - immunology; Macaca mulatta - immunology; Malaria Vaccines - adverse effects; Malaria Vaccines - immunology; Membrane Proteins - immunology; Merozoite Surface Protein 1 - adverse effects; Merozoite Surface Protein 1 - immunology; Plasmodium falciparum - immunology; Protozoan Proteins - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.10.022

Abstract In an effort to broaden the immune response induced by the RTS,S/AS02A ,vaccine, we have evaluated the immunogenicity of the RTS,S antigen when combined with MSP142 and with AMA1, antigens derived from the asexual blood stage. The objectives of this study were (i) to determine whether MSP142 and AMA1 vaccines formulated with the AS02A Adjuvant System were safe and immunogenic in the rhesus monkey model; (ii) to investigate whether MSP142 or AMA1 induced immune interference to each other, or to RTS,S, when added singly or in combinations at a single injection site; (iii) in the event of immune interference, to determine if this could be reduced when antigens were administered at separate sites. We found that MSP142 and AMA1 were safe and immunogenic, eliciting antibodies, and Th1 and Th2 responses using IFN-γ and IL-5 as markers. When malaria antigens were delivered together in one formulation, MSP142 and RTS,S reduced AMA1-specific antibody responses as measured by ELISA however, only MSP142 lowered parasite growth inhibitory activity of anti-AMA1 antibodies as measured by in vitro growth inhibition assay. Unlike RTS,S, MSP142 significantly reduced AMA1 IFN-γ and IL-5 responses. MSP142 suppression of AMA1 IFN-γ responses was not seen in animals receiving RTS,S + AMA1 + MSP142 suggesting that RTS,S restored IFN-γ responses. Conversely, AMA1 had no effect on MSP142 antibody and IFN-γ and IL-5 responses. Neither AMA1 alone or combined with MSP142 affected RTS,S antibody or IFN-γ and IL-5 responses. Immune interference by MSP142 on AMA1 antibody responses was also evident when AMA1, MSP142 and RTS,S were administered concurrently at separate sites. These results suggest that immune interference may be complex and should be considered for the design of multi-antigen, multi-stage vaccines against malaria.