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Infection and Immunity, January 2010, p. 486-494, Vol. 78, No. 1
0019-9567/10/$12.00+0     doi:10.1128/IAI.01359-08
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Toward the Rational Design of a Malaria Vaccine Construct Using the MSP3 Family as an Example: Contribution of Antigenicity Studies in Humans{triangledown} ,{dagger}

Corine G. Demanga,1 Lena-Juliette Daher,1,2 Eric Prieur,1 Catherine Blanc,1 Jean-Louis Pérignon,1 Hasnaa Bouharoun-Tayoun,2 and Pierre Druilhe1*

Biomedical Parasitology Unit, Institut Pasteur, Paris, France,1 Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon2

Received 6 November 2008/ Returned for modification 20 January 2009/ Accepted 20 October 2009

Plasmodium falciparum merozoite surface protein (MSP3) is a main target of protective immunity against malaria that is currently undergoing vaccine development. It was shown recently to belong, together with MSP6, to a new multigene family whose C-terminal regions have a similar organization, 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 four proteins of the MSP3 family using four recombinant proteins and 24 synthetic peptides. Antibodies to each MSP3 family antigen were found to be 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, although with an overall predominance of the IgG3 subclass. Human antibodies affinity purified upon each of the 24 peptides exerted an antiparasite antibody-dependent cellular inhibition 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 these findings and those from related immunogenicity studies in mice and demonstrated 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.

* Corresponding author. Mailing address: Biomedical Parasitology Unit, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 331 45 68 85 78. Fax: 331 45 68 86 40. E-mail: druilhe{at}pasteur.fr

{triangledown} Published ahead of print on 2 November 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.

Infection and Immunity, January 2010, p. 486-494, Vol. 78, No. 1
0019-9567/10/$12.00+0     doi:10.1128/IAI.01359-08
Copyright © 2010, American Society for Microbiology. All Rights Reserved.





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