Designing Malaria Vaccines to Circumvent Antigen Variability

Vaccine. 2015 Dec 22;33(52):7506-12. doi: 10.1016/j.vaccine.2015.09.110. Epub 2015 Nov 1.

Abstract

Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.

Keywords: Allele-specific efficacy; Cross-protection; Diversity; Heterologous; Malaria; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigenic Variation*
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Cross Protection*
  • Humans
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control*
  • Malaria Vaccines / genetics*
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Plasmodium falciparum / chemistry
  • Plasmodium falciparum / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Sporozoites / immunology
  • Vaccines, Attenuated / immunology
  • Vaccines, Subunit / immunology

Substances

  • Antigens, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Vaccines, Attenuated
  • Vaccines, Subunit