Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double-blind randomized controlled clinical trial.
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.
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Else M
EM
Bijker
Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC Leiden, The Netherlands.
Remko
R
Schats
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Joshua M
JM
Obiero
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Marije C
MC
Behet
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Geert-Jan
GJ
van Gemert
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Marga
M
van de Vegte-Bolmer
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Wouter
W
Graumans
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.
Lisette
L
van Lieshout
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Guido J H
GJ
Bastiaens
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Karina
K
Teelen
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Cornelus C
CC
Hermsen
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Anja
A
Scholzen
Leiden University Medical Center, Department of Infectious Diseases, PO Box 9600, 2300 RC Leiden, The Netherlands.
Leo G
LG
Visser
Radboud university medical center, Department of Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Robert W
RW
Sauerwein
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000962:Antimalarials / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002738:Chloroquine / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000032:analysis; D004311:Double-Blind Method; D004912:Erythrocytes / Q000469:parasitology; D053804:Granzymes / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology; D034101:Sporozoites / Q000276:immunology*; D055815:Young Adult
D000906:Antibodies; D000962:Antimalarials; D016054:DNA, Protozoan; D052118:Lysosomal-Associated Membrane Protein 1; D002738:Chloroquine; D053804:Granzymes; D015767:Mefloquine