New article...which might be the reason shares jumped to 3 last week..
Inducing humoral and cellular responses to multiple sporozoite and liver stage malaria antigens using pDNA
Infect Immun. 2013 Jul 29. [Epub ahead of print]
Inducing humoral and cellular responses to multiple sporozoite and liver stage malaria antigens using pDNA.
Ferraro B, Talbott KT, Balakrishnan A, Cisper N, Morrow MP, Hutnick NA, Myles DJ, Shedlock DJ, Obeng-Adjei N, Yan J, Kayatani A, Richie N, Cabrera W, Shiver R, Khan AS, Brown AS, Yang M, Wille-Reece U, Birkett AJ, Sardesai NY, Weiner DB.
Source
University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA, 19104.
Abstract
A vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Plasmodium falciparum (Pf) malaria, however, a technology for formulating and delivering such a vaccine has remained elusive. Here, we report the preclinical assessment of an optimized DNA vaccine approach that targets four Pf antigens: circumsporozoite protein (CSP), liver stage antigen 1 (LSA1), thrombospondin-related-anonymous-protein (TRAP), and cell-traversal protein for ookinetes and sporozoites (CelTOS). Synthetic DNA sequences were designed for each antigen with modifications to improve expression, and were delivered using in vivo electroporation (EP). Immunogenicity was evaluated in mice and non-human primates (NHPs) and assessed by ELISA, IFN? ELISpot, and flow cytometry. In mice, DNA+EP delivery induced antigen-specific IFN? production as measured by ELISpot and IgG seroconversion against all antigens. Sustained production of IFN?, IL-2 and TNFa was elicited in both the CD4+ and CD8+ T cell compartments. Furthermore, hepatic CD8+ lymphocytes produced LSA1-specific IFN?. The immune responses conferred in mice by this approach translated to the NHP model showing cellular responses by ELISPOT assay and intracellular cytokine staining. Notably, antigen-specific CD8+ Granzyme B+
