Towards a synthetic malaria vaccine: cyclization of a peptide eliminates the production of parasite-unreactive antibody.

Abstract

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.

• Authors: H M Etlinger, A Trzeciak
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (Philos Trans R Soc Lond B Biol Sci) Vol. 340 Issue 1291 Pg. 69-72 (Apr 29 1993) ISSN: 0962-8436 [Print] England
• PMID: 8099745 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Protozoan Proteins
• Protozoan Vaccines
• Vaccines, Synthetic
• circumsporozoite protein, Protozoan

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Monoclonal
• Humans
• Immunoglobulin G (classification, immunology)
• Malaria, Falciparum (immunology, prevention & control)
• Mice
• Mice, Inbred BALB C (immunology)
• Molecular Sequence Data
• Plasmodium falciparum (immunology)
• Protozoan Proteins (immunology)
• Protozoan Vaccines
• Vaccines, Synthetic