Etlinger H M, Trzeciak A
Pharmaceutical Research New Technologies, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
Philos Trans R Soc Lond B Biol Sci. 1993 Apr 29;340(1291):69-72. 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.
