The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab-restricted: possible implications for malaria vaccines.
The immunogenicity of a novel synthetic peptide consisting of an average of 40 (Asn-Ala-Asn-Pro) repeats of the circumsporozoite protein of Plasmodium falciparum, (NANP)40, was studied in mice without using any carrier proteins. First, high titers of anti-(NANP)40 antibodies could be obtained after immunization of C57BL/6 mice. These antibodies also reacted with an extract of mosquitoes infected with P. falciparum sporozoites. C57BL/6 nu/nu mice did not produce antibodies against (NANP)40. Secondly, when 14 strains of mice with nine different H-2 haplotypes were immunized with (NANP)40 without carrier, only H-2b mice were found to produce anti-(NANP)40 antibodies, whereas all non-H-2b mice were consistently unresponsive. This response was demonstrated to be I-A-linked by using recombinant and mutant mice. I-Ab [B10.A(5R)] mice produced anti-(NANP)40 antibodies as well as H-2b inbred mice. B6CH-2bm12 I-Ab-mutant mice showed only a very low response. Third, the antibody response against (NANP)40 could be induced in nonresponder mice by immunization with the peptide coupled to a carrier protein. In view of the existence of such an exceptional H-2b restriction in the response to sporozoite synthetic peptides in mice, the triggering of peptide-specific T cell responses in humans receiving sporozoite malaria vaccines might be difficult to achieve.
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000941:Antigens; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014614:Vaccines, Synthetic