Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara.

Nereida Jiménez De Oya,Estela Escribano-Romero,Juan-Carlos Saiz,Juan García-Arriaza,Patricia Pérez,Mariano Esteban,Miguel A Martín-Acebes,Ana-Belén Blázquez

doi:10.3390/ph15030354

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain–Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.

Highlights

The potential of emerging viral diseases to cause massive outbreaks with devastating effects on human health and the economy has become clear by the SARS-CoV-2 pandemic that has highlighted the need to anticipate viral emergencies and the utility of safe and efficacious vaccines to control emerging viral diseases
We have previously shown that a Zika virus (ZIKV) vaccine candidate based on the highly attenuated poxvirus modified vaccinia virus Ankara (MVA) expressing ZIKV prM and E structural proteins (MVA-ZIKV) induced a robust specific protective immune response against ZIKV infection in mouse models [23,24]
The results reported here could indicate that failure of the MVA-ZIKV vaccine candidate to fully protect against West Nile virus (WNV)

Summary

Introduction

The potential of emerging viral diseases to cause massive outbreaks with devastating effects on human health and the economy has become clear by the SARS-CoV-2 pandemic that has highlighted the need to anticipate viral emergencies and the utility of safe and efficacious vaccines to control emerging viral diseases. One of the major concerns for the massive usage of ZIKV vaccines is that this possible cross-reactivity can lead, in other cases, to flavivirus-disease exacerbation by antibody-dependent enhancement (ADE). ADE occurs when suboptimal neutralizing or non-neutralizing crossreactive antibodies elicited in a primary infection with a flavivirus bind heterologous flavivirus particles during a subsequent infection This facilitates virus entry and infection into Fcγ receptor-bearing cells and promotes disease exacerbation. This phenomenon has been mainly associated to cross-reactive antibodies directed against prM and the fusion loop epitope within the E protein [11,12]. Anticipating the potential scenario of emergency vaccination against ZIKV in areas where WNV is circulating, such as some parts of Europe and the Mediterranean. Further work is needed to confirm these results in non-human primates, the present data support the safety profile of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic

Immunization with MVA-ZIKV Vaccine Candidate Does Not Affect WNV Infection

Vaccination with MVA-ZIKV Does Not Alter the WNV-Specific Humoral Response Elicited by WNV Infection

For experimental design, see panel (A) in Figure 1

Viruses

Mice Experiments

Antibody Analyses