Sporozoite immunization of human volunteers under chemoprophylaxis induces functional antibodies against pre-erythrocytic stages of Plasmodium falciparum.
BACKGROUND
Long-lasting and sterile protective immunity against Plasmodium falciparum can be achieved by immunization of malaria-naive human volunteers under chloroquine prophylaxis with sporozoites delivered by mosquito bites (CPS-immunization). Protection is mediated by sporozoite/liver-stage immunity. In this study, the capacity of CPS-induced antibodies to interfere with sporozoite functionality and development was explored.


METHODS
IgG was purified from plasma samples obtained before and after CPS-immunization from two separate clinical trials. The functionality of these antibodies was assessed in vitro in gliding and human hepatocyte traversal assays, and in vivo in a human liver-chimeric mouse model.


RESULTS
Whereas pre-treatment of sporozoites with 2 mg/ml IgG in the majority of the volunteers did not have an effect on in vitro sporozoite gliding motility, CPS-induced IgG showed a distinct inhibitory effect in the sporozoite in vitro traversal assay. Pre-treatment of P. falciparum sporozoites with post-immunization IgG significantly inhibited sporozoite traversal through hepatocytes in 9/9 samples when using 10 and 1 mg/ml IgG, and was dose-dependent, resulting in an average 16% and 37% reduction with 1 mg/ml IgG (p = 0.003) and 10 mg/ml IgG (p = 0.002), respectively. In vivo, CPS-induced IgG reduced liver-stage infection and/or development after a mosquito infection in the human liver-chimeric mouse model by 91.05% when comparing 11 mice receiving post-immunization IgG to 11 mice receiving pre-immunization IgG (p = 0.0008).


CONCLUSIONS
It is demonstrated for the first time that CPS-immunization induces functional antibodies against P. falciparum sporozoites, which are able to reduce parasite-host cell interaction by inhibiting parasite traversal and liver-stage infection. These data highlight the functional contribution of antibody responses to pre-erythrocytic immunity after whole-parasite immunization against P. falciparum malaria.
Marije C
MC
Behet
Lander
L
Foquet
Geert-Jan
GJ
van Gemert
Else M
EM
Bijker
Philip
P
Meuleman
Geert
G
Leroux-Roels
Cornelus C
CC
Hermsen
Anja
A
Scholzen
Radboud University Medical Center, Department of Medical Microbiology, Geert Grooteplein 28, Microbiology 268, Nijmegen, HB 6500, The Netherlands. Robert.Sauerwein@radboudumc.nl.
Robert W
RW
Sauerwein
D000328:Adult; D000818:Animals; D000852:Anopheles; D000913:Antibodies, Protozoan / Q000276:immunology; D000962:Antimalarials / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D034101:Sporozoites / Q000254:growth & development / Q000276:immunology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000962:Antimalarials; D017780:Malaria Vaccines; D002738:Chloroquine