Investigation of immune response induction by Japanese encephalitis live-attenuated and chimeric vaccines in mice

MedComm (2020). 2022 Apr 6;3(2):e117. doi: 10.1002/mco2.117. eCollection 2022 Jun.

Abstract

The Japanese encephalitis (JE) live-attenuated vaccine SA14-14-2 and the chimeric vaccine IMOJEV (JE-CV) are two kinds of vaccines available for use worldwide. JE-CV was previously known as ChimeriVax-JE, that consists of yellow fever vaccine 17D (YFV-17D) from which the structural genes (prM/E) have been replaced with those of SA14-14-2. This study aimed to investigate the neutralizing antibody, protection efficacy, and specific T-cell response elicited by both vaccines in mice. The neutralizing antibodies produced by JE-CV were slightly lower than those produced by SA14-14-2, but the protection conferred by JE-CV was considerably lower in the low vaccine dose immunization group. Furthermore, the JE-CV did not induce a specific T-cell response against JEV NS3, while it did induce a potent antigen-specific T-cell response against the viral backbone vaccine YFV. In conclusion, this study is the first detailed investigation of the cellular immune response to the two vaccines. Enzyme-linked immunospot (ELISPOT) and flow staining suggest a more potent specific T-cell response against the JEV antigen was elicited in mice immunized with SA14-14-2 but not JE-CV. Using heterologous flaviviruses as a live-attenuated vaccine backbone may unlikely generate an optimal T-cell response against the vaccine strain virus and might affect the protective efficacy.

Keywords: Japanese encephalitis; T‐cell responses; chimeric vaccine; live‐attenuated vaccine; neutralizing antibodies; protection.