Abstract

Despite numerous efforts to identify the molecular and cellular effectors of the adaptive immunity that induce a long-lasting immunity against dengue or Zika virus infection, the specific mechanisms underlying such protective immunity remain largely unknown. One of the major challenges lies in the high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating. In the context of such a pre-existing DENV immunity that can exacerbate ZIKV infection and disease, and given the lack of appropriate treatment for ZIKV infection, there is an urgent need to develop an efficient vaccine against DENV and ZIKV. Notably, whereas several ZIKV vaccine candidates are currently in clinical trials, all these vaccine candidates have been designed to induce neutralizing antibodies as the primary mechanism of immune protection. Given the difficulty to elicit simultaneously high levels of neutralizing antibodies against the different DENV serotypes, and the potential impact of pre-existing subneutralizing antibodies induced upon DENV infection or vaccination on ZIKV infection and disease, additional or alternative strategies to enhance vaccine efficacy, through T cell immunity, are now being considered. In this review, we summarize recent discoveries about cross-reactive B and T cell responses against DENV and ZIKV and propose guidelines for the development of safe and efficient T cell vaccines targeting both viruses.

Highlights

  • Functional Genetics of Infectious Diseases Unit, Institut Pasteur, 75015 Paris, France; CNRS UMR 2000–Génomique Évolutive, Modélisation et Santé, Institut Pasteur, 75015 Paris, France

  • We summarize recent discoveries about cross-reactive B and T cell responses against dengue virus (DENV) and Zika virus (ZIKV) and propose guidelines for the development of safe and efficient T cell vaccines targeting both viruses

  • Initially believed to only cause mild disease, the 2013–2014 and 2015 outbreaks in French Polynesia and Brazil clearly revealed that ZIKV causes neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in infants born to ZIKV-infected women [10,11,12,13]

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Summary

History

Zika virus (ZIKV) is a Flavivirus transmitted by Aedes species mosquitoes. It is a single positive-stranded RNA virus closely related to yellow fever virus (YFV), dengue virus (DENV) and. We address the most recent findings regarding the adaptive immune response against ZIKV, focusing on the effect of DENV pre-existing immunity on ZIKV infection, the underlying idea being to identify immunological parameters predictive of increased susceptibility or protection against ZIKV infection and disease. In this respect, we will review the current state of knowledge on the impact of anti-DENV antibodies on ZIKV infection and disease, and summarize the recent data on the potential role of T cells in DENV and ZIKV immunity, with the aim to promote a long lasting immune protection against these two viruses

Antibody Cross-Reactivity between Zika and Dengue Viruses
T Cell Responses against DENV and Prospects for a Vaccine
Conclusions
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