Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine

Abstract

24Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related 25 mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in 26 the Chinese national Expanded Program on Immunization since 2007. The recent 27 recognition of severe disease syndromes associated with ZIKV, and the identification of 28 ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential 29 interaction between the two. In this study, we showed that SA14-14-2 is protective against 30 ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive 31 immune responses to ZIKV; however, it was cellular immunity that predominantly 32 mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not 33 result in significant cross-protection, but did mediate antibody dependent enhancement in 34 vitro, though this did not have an adverse impact on survival. This study suggests that 35 SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. 36This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected 37 regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising 38 avenue into developing a novel bivalent vaccine against both ZIKV and JEV. 40Importance 43 Japanese encephalitis is a controllable disease in many countries in Asia, especially in 44 China, where many people have Japanese encephalitis virus (JEV) immunity due to 45 extensive JEV vaccination campaigns or natural exposure. Live-attenuated SA14-14-2 46 strain is a safe and effective vaccine recommended by the World Health Organization and 47 has been vaccinated more than 600 million doses since 1989. As the prevalence of Zika 48 virus (ZIKV) and rising risk in above regions, the cross-reactive immune response 49 between these two antigenically closely related flaviviruses, JEV and ZIKV, should also be 50 fully recognized, which is presumed to be based on those ambiguous cross-reactive 51 immunity between dengue virus and ZIKV. In this study, we found that JEV SA14-14-2 52 vaccine conferred cross-protection against ZIKV challenge in mice, which is mainly due to 53 cellular immunity rather than neutralizing antibody response. However, specific protective 54 components or cooperation between components warrant to be explored in subsequent 55 experiments. In conclusion, this study can provide important evidence for those who live in 56 JEV-endemic areas and are at risk for ZIKV infection.57 4 Introduction 58 Recently, Zika virus (ZIKV) has caused devastating outbreaks of fetal congenital 59 malformations in South and Central America and now transmitted in more than 70 60 countries, including many previously unaffected regions. ZIKV infection during pregnancy 61 increases the risk of neurological disorders in newborns (1), such as microcephaly. In 62 adults, ZIKV causes Guillain-Barré syndrome and other neurologic disorders (2). So far, 63 no specific vaccine or antiviral for prevention and treatment of Z...

Japanese Encephalitis Virus Vaccination Elicits Cross-Reactive HLA-Class I-Restricted CD8 T Cell Response Against Zika Virus Infection

“…It has been shown in Dengue virus infection, efficient CD8 T cells response is sufficient to inhibit ADE in infected mice. Our present study together with previous findings (18,24) all suggest that cross-reactive JEV-specific CD8 T cells are protective to ZIKV infection in wild-type mice that are not HLA-transgenic (18,19,25). Thus, JEV vaccine can be clinically used for the prevention of ZIKV infection and also is at low risk of ADE induction in immune-competent humans.…”