Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double-blind randomized controlled clinical trial

Else M Bijker; Remko Schats; Joshua M Obiero; Marije C Behet; Geert-Jan van Gemert; Marga van de Vegte-Bolmer; Wouter Graumans; Lisette van Lieshout; Guido J H Bastiaens; Karina Teelen; Cornelus C Hermsen; Anja Scholzen; Leo G Visser; Robert W Sauerwein

doi:10.1371/journal.pone.0112910

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.

Affiliations

¹ Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
² Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC Leiden, The Netherlands.
³ Leiden University Medical Center, Department of Medical Microbiology, PO Box 9600, 2300 RC Leiden, The Netherlands; Leiden University Medical Center, Department of Parasitology, PO Box 9600, 2300 RC Leiden, The Netherlands.

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

Grants and funding

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.