IAI Accepts, published online ahead of print on 2 November 2009

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Infect. Immun. doi:10.1128/IAI.01359-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Towards the Rational Design of a Malaria Vaccine Construct; Example of the MSP3 Family, Part II: Antigenicity Studies

Corine G. Demanga, Lena-Juliette Daher, Eric Prieur, Catherine Blanc, Jean-Louis Pérignon, Hasnaa Bouharoun-Tayoun, and Pierre Druilhe^*

Biomedical Parasitology Unit, Institut Pasteur, Paris, France; Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon

^* To whom correspondence should be addressed. Email: druilhe{at}pasteur.fr.

Plasmodium falciparum MSP3 is a main target of protective immunity against malaria, currently undergoing vaccine development. It was shown recently to belong, together with MSP6, to a new multigene family, which C-terminal regions have a similar organisation, contain both homologous and divergent regions, and are highly conserved across isolates. In an attempt to rationally design novel vaccine constructs, we extended the analysis of antigenicity and function of region-specific antibodies, previously performed with MSP3 and MSP6, to the remaining 4 proteins of the MSP3 family using 4 recombinant proteins and 24 synthetic peptides. Antibodies to each MSP3 family antigen were found highly prevalent among malaria exposed individuals from the village of Dielmo (Senegal). Each of the 24 peptides was antigenic, defining at least one epitope mimicking that of the native proteins, with a distinct IgG isotype pattern for each, though with an overall predominance of the IgG3 subclass. Human antibodies affinity-purified upon each of the 24 peptides exerted an anti-parasite ADCI effect, which in most cases was as strong as that of IgG from protected African adults. The two regions with high homology were found to generate a broad network of cross-reactive antibodies with various avidities. A first multigenic construct was designed using the above findings and those from related immunogenicity studies in mice, and was shown to have valuable immunological properties. These results indicate that numerous regions from the MSP3 family play a role in protection and provide a rationale for the tailoring of new MSP3 derived malaria vaccines.