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.