Recent advances in understanding the adaptive immune response to Zika virus and the effect of previous flavivirus exposure

Abstract

Zika virus (ZIKV) caused explosive epidemics across the Americas, starting in Brazil in 2015, and has been associated with severe manifestations such as microcephaly in babies born to infected mothers and Guillain-Barré syndrome in adults. As the underlying mechanisms of pathogenesis remain largely unknown, diverse investigations have focused on a potential role for flavivirus cross-reactive antibodies in enhancing ZIKV infection. Antibody-dependent enhancement is especially concerning due to structural similarities between ZIKV and other flaviviruses, especially dengue virus (DENV), that co-circulate in areas affected by ZIKV. Conversely, investigating cross-neutralizing antibodies is important for understanding protection among flaviviruses, including ZIKV. In this review, we discuss the latest findings regarding ZIKV-induced adaptive immunity, such as monoclonal and polyclonal antibody responses, structural immunology, and T cell-mediated responses. Much progress has been made in a short amount of time, but many questions remain. Fully understanding the specificity, magnitude, and kinetics of B cell/antibody and T cell responses in ZIKV-infected individuals with or without prior exposure to flaviviruses is of great relevance for diagnostics and vaccine development.

A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates

“…ZIKV antibodies can cross-react with DENV and cause DENV enhancement in animal models. Therefore, it is anticipated that developing safe and effective ZIKV vaccines may be challenging (Andrade and Harris, 2018; George et al, 2017; Stettler et al, 2016). …”

“…It is possible that dengue enhancement would also be mediated by cross-reactive antibodies elicited by vacci-nation against ZIKV (Andrade and Harris, 2018; George et al, 2017; Stettler et al, 2016). Because of this uncertainty, passive antibody administration for protection against ZIKV may represent a safe and practical alternative to vaccination during pregnancy and for infants and travelers, since antibodies can be engineered to prevent enhancement and have greatly extended half-lives by incorporating known Fc mutations (Gautam et al, 2018; Griffin et al, 2017; Ko et al, 2014; Robbie et al, 2013; Zalevsky et al, 2010) (https://www.clinicaltrials.gov identifier NCT02878330).…”

Association of past dengue fever epidemics with the risk of Zika microcephaly at the population level in Brazil

“…ZIKV and DENV cross-immunity can be either protective or enhancing in experimental models. However, many questions still need to be addressed, particularly by placing in vitro and in vivo findings in an epidemiological context 29,30 . In this article, we analyse the interaction between dengue fever epidemics from 2001 to 2014 and the 2015/2016 microcephaly epidemic in 400 microregions in Brazil.…”

A Bioinformatic Glimpse of Human-Origin Zika Virus Polyprotein

“…ZIKV is known to induce antibody-mediated and cell-mediated immunological responses [13,14]. Most significant to the bioinformatic parameters reported here, polyprotein amino acid 1118 is a component of a putative 20-mer conformational epitope (CE6) that has been reported [15] for polyprotein amino acids 1105-1124.…”