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Infect Immun 2010 Nov;78(11):4613-24

Multiple antigen peptide vaccines against Plasmodium falciparum malaria.

Mahajan B, Berzofsky JA, Boykins RA, Majam V, Zheng H, Chattopadhyay R, de la Vega P, Moch JK, Haynes JD, Belyakov IM, Nakhasi HL, Kumar S

Abstract

Multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver-stage and blood-stage of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J), one congenic (HLA-A2 on the C57BL/6 background) and one outbred (CD1) strains of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1 and MAP-3 had an anti-parasite effect that was also dependent on the mouse MHC background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of P. falciparum sporozoites in HepG2 liver cells (highest 95.16% in HLA-A2 C57BL/6; lowest 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with MAP-2 (PfCSP, PfLSA-1, PfMSP-142 and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA and PfMSP-142) vaccines were able to reduce the growth of blood stage parasites in erythrocytes cultures to varying degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant the further development, preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by HLA- divergent populations from around the world.


Category: Journal Article
PubMed ID: #20823210 DOI: 10.1128/IAI.00533-10
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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