Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development

PLoS One. 2015 Aug 20;10(8):e0136109. doi: 10.1371/journal.pone.0136109. eCollection 2015.

Abstract

Background: Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified.

Methodology: Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens.

Conclusions: These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates.

Trial registration: ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology*
  • Erythrocytes / immunology*
  • Erythrocytes / parasitology
  • Humans
  • Immunization
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / parasitology
  • Malaria Vaccines / immunology*
  • Malaria Vaccines / pharmacology
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / immunology
  • Rabbits
  • Sporozoites / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / parasitology

Substances

  • Antigens, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins

Associated data

  • ClinicalTrials.gov/NCT00392015
  • ClinicalTrials.gov/NCT00870987

Grant support

This work was supported by Military Infectious Diseases Research Program Work Unit Number 602278A 870S A1209 https://midrp.amedd.army.mil; and PATH Malaria Vaccine Initiative Number GAT.0888-11-08533-COL http://www.malariavaccine.org Camris International, Technical Resources International, Inc. EMD Millipore Corporation, provided support in the form of salaries for authors JCA, JW, and JKM retrospectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.