Journal of Vaccines & Vaccination

A synthetic multi-antigen approach targeting Plasmodium falciparum malaria

4^th International Conference on Vaccines & Vaccination

September 24-26, 2014 Valencia Convention Centre, Spain

Ferraro B, Espinosa D A, Balakrishnan A, Reuschel E L, Morrow M P, Hutnick N A, Obeng-Adjei N, Yan J, Khan A S, Yang M, Brown A S, Wille-Reece U, Birkett A, Sardesai N Y, Zavala F and Weiner D B

Scientific Tracks Abstracts: J Vaccines Vaccin

Abstract:

P . falciparum (Pf) malaria remains a significant public health problem. Current evidence suggests a vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Pf malaria. Here, we report the preclinical assessment of a DNA vaccine approach that targets four Pf antigens: CSP, LSA1, TRAP, and CelTOS (MAV4). Synthetic DNA sequences were designed and delivered using electroporation (EP). In mice, DNA+EP delivery induced robust cellular and humoral immune responses. Further, hepatic CD8 + T cells produced antigen-specific IFNγ. A chimeric Pf-Plasmodium berghei (Pb) CSP sporozoite challenge model, a Pb sporozoite that contains Pf CSP in place of Pb CSP, was used to evaluate if immune responses induced by the Pf CSP component of MAV4 could decrease liver-stage parasite burden. Immunization with the synthetic pDNA Pf CSP resulted in a significant decrease in liver- stage levels. In Rhesus macaques, MAV4 elicited robust antibody and T cell responses to all antigens. Notably, the phenotype of the majority of antigen-specific CD8 + T cells indicated potential for cytotoxic and effector functions. In conclusion, DNA+EP delivery elicits strong immune responses against multiple malaria antigens and merits further study in clinical trials.