Cutaneous Delivery of a Live, Attenuated Chimeric Flavivirus Vaccines against Japanese Encephalitis (ChimeriVaxTM-JE) in Non-Human Primates

Abstract

Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an urgent need for alternative technologies for mass vaccination against these and other diseases, particularly in the developing world. Here, we administered a live attenuated, chimeric JE vaccine (ChimeriVaxTM-JE) to non-human primates by skin microabrasion and intradermal delivery using microneedles. Both cutaneous delivery methods induced mild viremia similar in magnitude to that observed following subcutaneous (SC) injection. The duration of viremia induced by cutaneous delivery (5-7 days), however, was substantially longer than via SC (0-3 days). In addition, mean neutralizing antibody titers in cutaneous delivery groups were up to 7-fold greater than via SC injection. There were no safety issues identified and both cutaneous delivery methods appeared to be well tolerated. Thus, cutaneous delivery may represent a minimally-invasive alternative approach for flavivirus vaccines that more closely resembles the natural route of viral infection.