A malaria vaccine candidate based on a hepatitis B virus core platform.
OBJECTIVE
The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes.


METHODS
Well-characterized CSP-specific neutralizing B cell epitopes and a 'universal' T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate.


RESULTS
The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems.


CONCLUSIONS
These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
Sällberg
Matti
M
Division of Clinical Virology, Karolinska Institute, Stockholm, Sweden.
Hughes
Janice
J
Jones
Joyce
J
Phillips
Tom R
TR
Milich
David R
DR
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D007114:Immunization; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D020449:Repetitive Sequences, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000913:Antibodies, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan