Novel Vaccine Technologies and Strategies to Promote Sustained Vaccine Efficiency

The overarching objective of this proposal is the identification of novel vaccination regimen sleading to improved malaria vaccine efficacyThe medical need for such a vaccine remains compellingTo accomplish this goaltwo attenuatedheterologous viral vaccine vectorsrecombinant vesicular stomatitis virusrVSVand recombinant Isfahan virusrISFVabundantly expressing Plasmodium falciparum circumsporozoite surface proteinCSPwill be generated and characterized in vitroSpecific AimVector safety will be confirmed in a mouse intracranial neurovirulence modelSpecific Aimand CSP specific immune responses will be assessed in mice to determine an optimal heterologous prime boost vaccination regimenSpecific AimBoth vectors are attenuated and replication competentthey are serologically distinct and phylogenetically divergentreducing potential immunological cross reactivity between themWe expect that both vectors used in heterologous prime boost vaccination regimenswill elicit very robust and durable CSP specific cellular and humoral immune responsesBecause current malaria vaccines have demonstrated only modest protection from diseasenew and improved malaria vaccines and vaccine regimens are urgently needed to protect the millions of people at risk from this widespread and deadly disease