Peculiarities of Zika Immunity and Vaccine Development: Lessons from Dengue and the Contribution from Controlled Human Infection Model.

Helton C Santiago,Tertuliano A Pereira-Neto,Ana C B Terzian,Anna P Durbin,Marcela H Gonçalves-Pereira

doi:10.3390/pathogens11030294

Abstract

The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV. Here, we discuss ZIKV vaccine development with the perspective of the immunological concerns implicated by DENV-ZIKV cross-reactivity and the use of a controlled human infection model (CHIM) as a tool to accelerate vaccine development.

Highlights

Zika virus (ZIKV) was initially isolated from a rhesus macaque in the Zika forest of Uganda in 1947 [1]
The first major outbreak of ZIKV was reported from the Island of Yap in Micronesia in 2007 where it was estimated that 72.6% of the population
Multifunctional T cell responses and cellular immunity have been considered important mechanisms for host resistance against other flaviviruses like dengue virus (DENV) [51,65] and immunity to yellow fever (YFV) [66–68]. Another important factor to consider in immunity against ZIKV and other flavivirus infections is the cross-reactivity of the immune response

Summary

Introduction

Zika virus (ZIKV) was initially isolated from a rhesus macaque in the Zika forest of Uganda in 1947 [1]. In March of 2014, Chilean public health authorities confirmed that ZIKV infection was detected in cases reported in February, concurrent with the circulation of the virus in French Polynesia [9]. A new immunological survey of undergraduate students using humoral and cellular tests has identified ZIKVpositivity in more than 80% of samples that could at least partially differentiate DENV and ZIKV infections [17]. These numbers are not far from those reported in Brazil, where a serological survey estimated that ZIKV seroprevalence exceeded 60% in Salvador

Clinical Presentation

Immune Responses

Implications of Flaviviruses Immunity on ZIKV Vaccine Development

Findings

Conclusions