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

  • Healy, Sara A1, 2, 3
  • Murphy, Sean C1, 4, 5
  • Hume, Jen C C1, 3
  • Shelton, Lisa1
  • Kuntz, Steve6
  • Van Voorhis, Wesley C5, 6
  • Moodie, Zoe7
  • Metch, Barbara7
  • Wang, Ruobing1
  • Silver-Brace, Tiffany1
  • Fishbaugher, Matthew1
  • Kennedy, Mark1
  • Finney, Olivia C1
  • Chaturvedi, Richa1
  • Marcsisin, Sean R8
  • Hobbs, Charlotte V3
  • Warner-Lubin, Margaret1, 9
  • Talley, Angela K1
  • Wong-Madden, Sharon1, 3
  • Stuart, Ken1
  • And 4 more
  • 1 Center for Infectious Disease Research, Seattle, Washington, USA.
  • 2 Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Washington, Seattle, Washington, USA.
  • 3 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • 4 Department of Laboratory Medicine and Microbiology, University of Washington, Seattle, Washington, USA.
  • 5 Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
  • 6 Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
  • 7 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • 8 Military Malaria Research Program, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • 9 C3 Research Associates, Seattle, Washington, USA.
  • 10 Department of Epidemiology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Published Article
Clinical Infectious Diseases
Oxford University Press
Publication Date
Sep 12, 2020
DOI: 10.1093/cid/ciz1010
PMID: 31621832


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.

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