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

被引:43
作者
Arevalo-Herrera, Myriam [1 ,2 ]
Forero-Pena, David A. [1 ,3 ]
Rubiano, Kelly [1 ,3 ]
Gomez-Hincapie, Jose [1 ,3 ]
Martinez, Nora L. [1 ,3 ]
Lopez-Perez, Mary [1 ,3 ]
Castellanos, Angelica [1 ,3 ]
Cespedes, Nora [1 ,2 ,3 ]
Palacios, Ricardo [4 ]
Onate, Jose Millan [5 ]
Herrera, Socrates [1 ,3 ]
机构
[1] Malaria Vaccine & Drug Dev Ctr MVDC, Cali, Colombia
[2] Univ Valle, Sch Hlth, Cali, Colombia
[3] CSRC, Cali, Colombia
[4] Merid R&D, Sao Paulo, Brazil
[5] Ctr Med Imbanaco, Cali, Colombia
关键词
DUFFY-BINDING-PROTEIN; CIRCUMSPOROZOITE PROTEIN; ANOPHELES-ALBIMANUS; PROTECTIVE EFFICACY; VACCINE CANDIDATE; AOTUS MONKEYS; IMMUNOGENICITY; FALCIPARUM; RESPONSES; RECEPTOR;
D O I
10.1371/journal.pone.0099754
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页数:12
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