Assessment in mice of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, P. falciparum.
The anti-P. falciparum sporozoite vaccine consisting of the synthetic peptide, Ac-Cys-(NANP)3, conjugated to the protein tetanus toxoid (TT), [Ac-Cys-(NANP)3]25-TT, is currently undergoing human trials. The purpose of the present study was to assess various immunological parameters of this vaccine in mice, which have practical implications in humans. Two injections of [Ac-Cys-(NANP)3]25-TT adsorbed to Al(OH)3 were required to elicit a high antibody response against both Ac-Cys-(NANP)3 and TT. The vaccine initiated equivalent Ac-Cys-(NANP)3 priming for a secondary IgG response in 1-week-old and adult mice. Immunization of female mice with TT or [Ac-Cys-(NANP)3]23-TT prior to mating resulted in offspring that passively received anti-Ac-Cys-(NANP)3 and/or anti-TT antibody and that had reduced secondary responses to Ac-Cys-(NANP)3 and TT. Tertiary challenge with vaccine could substantially overcome such inhibition. Preimmunization of adult mice with TT resulted in a specific inhibition of the anti-Ac-Cys-(NANP)3 antibody response that disappeared following tertiary challenge with the vaccine. The conjugate initiated an antibody response against Ac-Cys-(NANP)3 and TT in mice of 16 different genotypes; only very low T-cell proliferative responses to (NANP)3 were observed for some of these strains. Mice injected with (NANP)3 coupled to protein demonstrated a secondary response to Ac-Cys-(NANP)3 when challenged with (NANP)3 on a heterologous carrier, indicating that B-cell priming alone may be sufficient for a secondary antibody response. These results demonstrate that the vaccine has favourable and unfavourable characteristics in mice; the potential for both exists in humans.
D000375:Aging / Q000276:immunology; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000941:Antigens / Q000276:immunology*; D005260:Female; D007112:Immunity, Maternally-Acquired; D007156:Immunologic Memory; D036341:Intercellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000913:Antibodies, Protozoan; D000941:Antigens; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; C056967:acetylcysteine(asparaginyl-alanyl-asparaginyl-proline)3