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

Authors
  • 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.
Type
Published Article
Journal
Clinical Infectious Diseases
Publisher
Oxford University Press
Publication Date
Sep 12, 2020
Volume
71
Issue
6
Pages
1481–1490
Identifiers
DOI: 10.1093/cid/ciz1010
PMID: 31621832
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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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