Incorporation of T and B epitopes of the circumsporozoite protein in a chemically defined synthetic vaccine against malaria.
We show here an effective and novel approach to engineer peptide-based vaccines using a chemically defined system, known as multiple peptide antigen systems (MAPs), to protect an inbred mouse strain from infection against rodent malaria. 10 mono- and di-epitope MAP models containing different arrangements and stoichiometry of functional B and/or T helper cell epitopes from the circumsporozoite protein of Plasmodium berghei were used to immunize A/J mice. While these mice did not respond to the mono-epitope MAP bearing only the B or T epitope, very high titers of antibody and protective immunity against sporozoite challenge were elicited by di-epitope MAPs, particularly those with the B and T epitopes in tandem and present in equimolar amounts. These results, obtained in a well-defined rodent malaria model, indicate that MAPs may overcome some of the difficulties in the development of synthetic vaccines, not only for malaria but also for other infectious diseases.
Rockefeller University, New York, New York 10021.
J P
JP
Tam
P
P
Clavijo
Y A
YA
Lu
V
V
Nussenzweig
R
R
Nussenzweig
F
F
Zavala
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000138:chemical synthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015195:Drug Design; D000939:Epitopes / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006239:Haplotypes; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines; D014614:Vaccines, Synthetic
D000953:Antigens, Protozoan; D000939:Epitopes; D006183:H-2 Antigens; D009842:Oligopeptides; D015800:Protozoan Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan