4.6 Article

Plasmodium vivax Sporozoite Challenge in Malaria-Naive and Semi-Immune Colombian Volunteers

Journal

PLOS ONE
Volume 9, Issue 6, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0099754

Keywords

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Funding

  1. National Heart, Lung and Blood Institute (NHLBI) [5R01HL086488]
  2. Colombian National Research Council, COLCIENCIAS [527-2009, 529-2009, 360-2012, 458-2012]

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Background: Significant progress has been recently achieved in the development of Plasmodium vivax challenge infections in humans, which are essential for vaccine and drug testing. With the goal of accelerating clinical development of malaria vaccines, the outcome of infections experimentally induced in naive and semi-immune volunteers by infected mosquito bites was compared. Methods: Seven malaria-naive and nine semi-immune Colombian adults (n = 16) were subjected to the bites of 2-4 P. vivax sporozoite-infected Anopheles mosquitoes. Parasitemia levels, malaria clinical manifestations, and immune responses were assessed and compared. Results: All volunteers developed infections as confirmed by microscopy and RT-qPCR. No significant difference in the prepatent period (mean 12.5 and 12.8 days for malaria-naive and malaria-exposed, respectively) was observed but naive volunteers developed classical malaria signs and symptoms, while semi-immune volunteers displayed minor or no symptoms at the day of diagnosis. A malaria-naive volunteer developed a transient low submicroscopic parasitemia that cured spontaneously. Infection induced an increase in specific antibody levels in both groups. Conclusion: Sporozoite infectious challenge was safe and reproducible in semi-immune and naive volunteers. This model will provide information for simultaneous comparison of the protective efficacy of P. vivax vaccines in naive and semi-immune volunteers under controlled conditions and would accelerate P. vivax vaccine development.

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