Towards a Synthetic Malaria Vaccine: Cyclization of a Peptide Eliminates the Production of Parasite-Unreactive Antibody

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 340; no. 1291; pp. 69 - 72
• Main Authors: Etlinger, Howard M., Trzeciak, Arnold
• Format: Journal Article
• Language: English
• Published: London The Royal Society 29.04.1993; Royal Society of London
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies, Monoclonal; Antigens; Biological and medical sciences; Epitopes; Human protozoal diseases; Humans; Immunoglobulin G - classification; Immunoglobulin G - immunology; Infectious diseases; Malaria; Malaria vaccine; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Medical sciences; Mice; Mice, Inbred BALB C - immunology; Molecular Sequence Data; Monoclonal antibodies; Parasites; Parasitic diseases; Pathogens; Plasmodium falciparum - immunology; Protozoal diseases; Protozoan Proteins - immunology; Protozoan Vaccines; Reactivity; Sporozoites; Vaccination; Vaccines, Synthetic; Protozoa; Antimalarial; Cyclic peptides; Rodentia; Vaccine; Monoclonal antibody; Plasmodium falciparum; Vertebrata; Mammalia; Synthetic product; Antigenicity; Mouse; Sporozoa
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.1993.0049

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.