Report of a Consultation on the Optimization of Clinical Challenge Trials for Evaluation of Candidate Blood Stage Malaria Vaccines, 18-19 March 2009, Bethesda, MD, USA

Initiative for Vaccine Research, Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
Vaccine (Impact Factor: 3.49). 09/2009; 27(42):5719-25. DOI: 10.1016/j.vaccine.2009.07.049
Source: PubMed

ABSTRACT Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

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    • "For erythrocytic antigens this has been an issue as well because -until recently -it was ethically inconceivable to challenge human volunteers with malaria-infected blood due to the risk of transmitting life threatening blood borne diseases. However, extensive testing of the blood source used for the challenge has allowed a limited challenge study with the understanding that significant improvements are needed before blood challenges can be performed routinely similar to the mosquito bite challenges (Moorthy et al., 2009). A final issue to consider is that blood stage challenge in humans may not fully predict the situation where an individual receives a blood stage vaccine followed by mosquito bite challenge, as the vaccine-induced immune responses may be edited (i.e., altered) by the sporozoite and the liver-stage infection. "
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