Effect of the malaria vaccine Combination B on merozoite surface antigen 2 diversity

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Christian FlückIngrid Felger

Abstract

Extensive genetic polymorphism is generally found in Plasmodium falciparum surface antigens. This poses a considerable obstacle to the development of a malaria vaccine. In order to assess possible effects of a polymorphic vaccine, we have analyzed the genetic diversity of parasites collected in the course of a phase 2b field trial of the blood stage vaccine Combination B in Papua New Guinea. The full-length 3D7 allele of the merozoite surface protein 2 (MSP2) was included in Combination B as one of three subunits. Vaccinees had a lower prevalence of parasites carrying a 3D7-type allele (corresponding to that in the vaccine) and selection appeared to favour the alternative FC27-type alleles resulting in a higher incidence of morbid episodes associated with FC27-type parasites. We sequenced MSP2 alleles detected in study participants after vaccination to identify breakthrough genotypes. Extensive genetic diversity of MSP2 was observed in both the repetitive and family-specific domains, but alleles occurring in vaccine recipients were no different from those found in placebo recipients. A phylogenetic analysis showed no clustering of 3D7-type breakthrough infections from vaccine recipients. The repeat unit present in the vaccine m...Continue Reading

References

Mar 22, 2000·The Journal of Peptide Research : Official Journal of the American Peptide Society·M OcampoM E Patarroyo
Feb 15, 2003·Trends in Parasitology·Ingrid FelgerHans Peter Beck
Sep 25, 2003·The Journal of Experimental Biology·Siddhartha MahantyLouis H Miller
Oct 27, 2004·Infection and Immunity·Christian FlückIngrid Felger

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Citations

May 7, 2009·Immunology and Cell Biology·Jack S Richards, James G Beeson
Mar 8, 2008·Expert Review of Vaccines·Johan Vekemans, W Ripley Ballou
Apr 1, 2008·Expert Opinion on Drug Discovery·Claudia A DaubenbergerNicole Westerfeld
Sep 23, 2008·Vaccine·Victoria C BarclayAndrew F Read
Nov 6, 2008·International Journal for Parasitology·Hans-Peter BeckWillie Weir
Aug 15, 2014·Frontiers in Immunology·Alyssa E Barry, Alicia Arnott
Jun 5, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Pabitra SahaArdhendu K Maji

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