Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection

Cell Microbiol. 2016 Dec;18(12):1739-1750. doi: 10.1111/cmi.12608. Epub 2016 May 27.

Abstract

The development of an effective malaria vaccine has remained elusive even until today. This is because of our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre-erythrocytic stage. To identify the antigen(s) recognized by these antibodies, a newly developed library of P. falciparum antigens was screened with the neutralizing sera. Antibodies from protected individuals recognized a broad antigenic repertoire of which three antigens, PfMAEBL, PfTRAP and PfSEA1 were recognized by most protected individuals. As a proof of principle, we demonstrated that anti-PfMAEBL antibodies block liver stage development in human hepatocytes. Thus, these antigens identified are promising targets for vaccine development against malaria.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Protozoan / biosynthesis*
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Antimalarials / therapeutic use
  • Chloroquine / therapeutic use
  • Cross Reactions
  • Gene Expression
  • Hepatocytes / drug effects
  • Hepatocytes / immunology
  • Hepatocytes / parasitology
  • Humans
  • Immune Sera / chemistry
  • Immunity, Humoral*
  • Malaria Vaccines / administration & dosage
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Peptide Library
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Sporozoites / immunology
  • Vaccination

Substances

  • Antibodies, Neutralizing
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Antimalarials
  • Immune Sera
  • MAEBL protein, Plasmodium falciparum
  • Malaria Vaccines
  • Peptide Library
  • Protozoan Proteins
  • Receptors, Cell Surface
  • SEA-1 protein, Plasmodium falciparum
  • thrombospondin-related adhesive protein, protozoan
  • Chloroquine