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.
Tam
J P
JP
Rockefeller University, New York, New York 10021.
Clavijo
P
P
Lu
Y A
YA
Nussenzweig
V
V
Nussenzweig
R
R
Zavala
F
F
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