Sporozoite Immunization of Human Volunteers Under Mefloquine Prophylaxis Is Safe, Immunogenic and Protective: A Double-Blind Randomized Controlled Clinical Trial

PLoS One. 2014 Nov 14;9(11):e112910. doi: 10.1371/journal.pone.0112910. eCollection 2014.

Abstract

Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection. Trial registration: ClinicalTrials.gov NCT01422954.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood
  • Antibodies / immunology
  • Antimalarials / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chloroquine / therapeutic use*
  • DNA, Protozoan / analysis
  • Double-Blind Method
  • Erythrocytes / parasitology
  • Granzymes / metabolism
  • Healthy Volunteers
  • Humans
  • Immunity, Cellular
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Mefloquine / therapeutic use*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / physiology
  • Sporozoites / immunology*
  • Young Adult

Substances

  • Antibodies
  • Antimalarials
  • DNA, Protozoan
  • Lysosomal-Associated Membrane Protein 1
  • Chloroquine
  • Granzymes
  • Mefloquine

Associated data

  • ClinicalTrials.gov/NCT01422954

Grant support

This trial was funded by The Netherlands Organisation for Health Research and Development (ZonMw, project 95110086) and the Dioraphte foundation (project 12010100). AS received an EMBO long-term fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.