The major discovery this year are as follows. 1. Showed that radiation attenuated sporozoites administered intravenously into NHP induced potent CD4 and CD8+ T cell responses in blood and liver. Established that a high frequency of NK cells in the liver secrete IFN-g in response to stimulation providing an additional effector cell for protection. Furthermore, showed that monocytes and dendritic cells present SPZ antigen to T cells. 2. Completed a phase I clinical trial assessing whether irradiated PfSPZ given by the IV route is safe and protective in a dose escalation study. 3. Showed that an attenuated malaria vaccine ( PfSPZ Vaccine) confers high level protection in humans following an experimental challenge with malaria infection. 4. Showed that the dose of the PfSPZ Vaccine is critical for mediating immunity and protection.
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|Kastenmuller, Kathrin; Espinosa, Diego A; Trager, Lauren et al. (2013) Full-length Plasmodium falciparum circumsporozoite protein administered with long-chain poly(IÃ½Ã½C) or the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice. Infect Immun 81:789-800|
|Epstein, J E; Tewari, K; Lyke, K E et al. (2011) Live attenuated malaria vaccine designed to protect through hepatic CD8Ã½Ã½Ã½ T cell immunity. Science 334:475-80|
|Tewari, Kavita; Flynn, Barbara J; Boscardin, Silvia B et al. (2010) Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and Î±DEC-CSP in non human primates. Vaccine 28:7256-66|