Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020 Sep 12

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Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs, such as primaquine, act against liver-stage parasites. Here, we evaluated CVac regimens using primaquine and/or chloroquine as the partner drug to discern whether blood-stage parasite exposure impacts protection against homologous controlled human malaria infection. In a Phase I, randomized, partial double-blind, placebo-controlled study of 36 malaria-naive adults, all CVac subjects received chloroquine prophylaxis and bites from 12-15 P. falciparum-infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received postexposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After a chloroquine washout, subjects, including treatment-naive infectivity controls, underwent homologous, PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days. No serious adverse events occurred. During CVac, all but 1 subject in the study remained blood-smear negative, while only 1 subject (primaquine/chloroquine arm) remained polymerase chain reaction-negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (P = .01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood-smear negative. CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine postexposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity. NCT01500980. Published by Oxford University Press for the Infectious Diseases Society of America 2019.

Citation

Sara A Healy, Sean C Murphy, Jen C C Hume, Lisa Shelton, Steve Kuntz, Wesley C Van Voorhis, Zoe Moodie, Barbara Metch, Ruobing Wang, Tiffany Silver-Brace, Matthew Fishbaugher, Mark Kennedy, Olivia C Finney, Richa Chaturvedi, Sean R Marcsisin, Charlotte V Hobbs, Margaret Warner-Lubin, Angela K Talley, Sharon Wong-Madden, Ken Stuart, Anna Wald, Stefan H Kappe, James G Kublin, Patrick E Duffy. Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Sep 12;71(6):1481-1490