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
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.
- SourceAvailable from: Elke Bergmann-Leitner
Malaria Parasites, 03/2012; , ISBN: 978-953-51-0326-4
- "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. "
- [Show abstract] [Hide abstract]
ABSTRACT: While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide “herd protection” by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5–17 months, and approximately 30% protection in children aged 6–12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide “herd protection” by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document.Vaccine 04/2013; 31:B233–B243. DOI:10.1016/j.vaccine.2013.02.040 · 3.49 Impact Factor
- Research in Immunology 01/1996; 147(8-9):587-95. DOI:10.1016/S0923-2494(97)85226-1