Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

S. V. Bardina et al., Science. 2017; 356(6334):175-180.

Speaker: Yu-San Kao（高于珊）                   Time: 14:00~15:00, Nov. 1, 2017

Commentator: Dr. Guey Chuen Perng（彭貴春 老師） Place: Room 601

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Antibody-dependent enhancement (ADE) has been implicated in more severe forms of flavivirus disease due to preexisting flavivirus immunity, and ZIKV is presently circulating in areas that DENV and West Nile virus (WNV) are highly endemic. Accordingly, as ZIKV continues to spread, understanding how preexisting flavivirus immunity impacts ZIKV pathogenesis is a high priority. Previous studies showed that some DENV antibodies are cross-reactive to ZIKV and can enhance ZIKV infection at specific concentrations using in vitro systems. However, enhancement of ZIKV infection by DENV antibodies in vivo was not well investigated. In this study, the authors used convalescent plasma from DENV and WNV infected individuals, and they confirmed that IgG elicited by infection with DENV and WNV is capable of mediating ADE of ZIKV through FcγR engagement in vitro. They further used Stat2−/− C57BL/6 mice which displayed considerable morbidity and mortality in response to ZIKA infection to establish the first animal model showing a direct correlation between ADE and fever. The data indicated that administration of DENV or WNV convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity and mortality, including fever, viremia, and viral loads in spinal cord and testes. To further understand the relationship between DENV and WNV antibody titers and the potential for enhanced ZIKV disease in vivo, they evaluated a range of doses for control, DENV, and WNV immune plasma and its subsequent effect on ZIKV infection. High concentrations of DENV immune plasma  resulted in protection against ZIKV infection, but on the other hand, in vivo enhancement may occur optimally at low concentrations of ZIKV-reactive IgG. Their results highlight the urgent need for epidemiological studies in humans to understand the impact of preexisting flavivirus antibodies for ZIKV-induced disease and sequelae, and emphasize the design and use of flavivirus vaccines in ZIKV affected areas with great caution.

References：

1. Priyamvada L et al., Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. Proc Natl Acad Sci U S A. 2016; 113(28):7