title: Pre-clinical assessment of novel multivalent MSP3 malaria vaccine constructs.
abstract: BACKGROUND
  MSP3 has been shown to induce protection against malaria in African children. The characterization of a family of Plasmodium falciparum merozoite surface protein 3 (MSP3) antigens sharing a similar structural organization, simultaneously expressed on the merozoite surface and targeted by a cross-reactive network of protective antibodies, is intriguing and offers new perspectives for the development of subunit vaccines against malaria.
  
  
  METHODS
  Eight recombinant polyproteins containing carefully selected regions of this family covalently linked in different combinations were all efficiently produced in Escherichia coli. The polyproteins consisted of one monovalent, one bivalent, one trivalent, two tetravalents, one hexavalent construct, and two tetravalents incorporating coiled-coil repeats regions from LSA3 and p27 vaccine candidates.
  
  
  RESULTS
  All eight polyproteins induced a strong and homogeneous antibody response in mice of three distinct genotypes, with a dominance of cytophilic IgG subclasses, lasting up to six months after the last immunization. Vaccine-induced antibodies exerted a strong monocyte-mediated in vitro inhibition of P. falciparum growth. Naturally acquired antibodies from individuals living in an endemic area of Senegal recognized the polyproteins with a reactivity mainly constituted of cytophilic IgG subclasses.
  
  
  CONCLUSIONS
  Combination of genetically conserved and antigenically related MSP3 proteins provides promising subunit vaccine constructs, with improved features as compared to the first generation construct employed in clinical trials (MSP3-LSP). These multivalent MSP3 vaccine constructs expand the epitope display of MSP3 family proteins, and lead to the efficient induction of a wider range of antibody subclasses, even in genetically different mice. These findings are promising for future immunization of genetically diverse human populations.
authors.affiliation: Malaria Vaccine Development Laboratory, Institut Pasteur, and Vac4all initiative, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bang
authors.forename: Eric
authors.initials: E
authors.lastname: Prieur
authors.forename: Christian
authors.initials: C
authors.lastname: Roussilhon
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000293:Adolescent; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium