University of Pennsylvania, USA
Bernadette Ferraro is R&D Scientist at Inovio Pharmaceuticals Inc.inSan Diego, CaliforniaResearch .she was published atricales and international journals
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.