Development of Chimeric Vesiculo/Alphaviruses as an Alphavirus Vaccine

Rose, John; Eldridge, John

Abstract

There is major public health concern about the continuing spread of alphaviruses such as chikungunya virus (CHIKV) that has caused major epidemics spreading from Africa and Southeast Asia to Europe. An ideal alphavirus vaccine would provide single-dose protection. A chimeric vaccine vector based on a defective vesicular stomatitis virus (VSV) deleted for its surface glycoprotein gene (G), and instead expressing the CHIKV envelope proteins induces high levels of CHIKV neutralizing antibodies and provides single-dose protection. The overall goal of this highly collaborative partnership is to preclinicaly validate this existing vaccine candidate as well as other highly attenuated VSV-vectored CHIKV vaccines in a recombinant VSV background that is already FDA-approved. The optimal rVSV/CHIKV vaccine candidate with the best combination of protective efficacy, manufacturability, attenuation, FDA familiarity, and clinical experience will then be selected. Thi candidate will be advanced through the development of compliant seed stocks documented to be appropriate for further manufacture under cGMP. In addition, this vaccine will be tested in non-human primates (NHPs) to confirm safety and efficacy, and a lyophilized formulation with the stability characteristics required for practical field use will be developed. General applicability of the platform for another emerging alphavirus will also be tested.

Public Health Relevance

Alphaviruses such as chikungunya virus cause serious disease in humans, yet there are no commercially available vaccines to prevent alphavirus infections. Development of a vaccine platform that would provide single-dose protection against chikungunya fever and other diseases caused by alphaviruses is a high biodefense priority. This project will support a partnership among two academic laboratories and one industrial partner to preclinically evaluate and develop a single-dose CHIKV vaccine appropriate for manufacturing, and also validate this vector platform for universal use against alphavirus infections.