Towards a synthetic malaria vaccine: cyclization of a peptide eliminates the production of parasite-unreactive antibody.
In a previous study, human beings were vaccinated with a P. falciparum malaria vaccine candidate consisting of tetanus toxoid coupled to linear (Asn-Ala-Asn-Pro)3 ((NANP)3). The vaccine initiated protection in some people, but some individuals mainly produced anti-peptide antibodies that did not react with the pathogen. A likely contributor to the formation of epitopes that give rise to pathogen-unreactive antibodies is the free terminal proline which is not a terminal residue in the native protein. To avoid the elicitation of antibodies against terminal epitopes, (NANP)3 was cyclized. In contrast to monoclonal antibodies to the linear peptide where 35% were unreactive with the parasite, all monoclonal antibodies to the cyclized peptide were found to react with the parasite.
Etlinger
H M
HM
Pharmaceutical Research New Technologies, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
Trzeciak
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan