Vaccine protection against Zika virus from Brazil

Abstract

Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas1,2. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans3–8 and mice9–11. The rapid development of a safe and effective ZIKV vaccine is a global health priority1,2, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice11. We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.

Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

“…In the viremia model [39,40], temoporfin treatment resulted in about 100-fold reduction in ZIKV-induced viremia in immunocompetent Balb/C mice compared to the vehicle control ( Figure 5A). In the lethal A129 mouse model [41,42], all the ZIKV-infected animals treated with vehicle died with typical neurological symptoms including hind limb weakness and paralysis.…”

Recent advances in human flavivirus vaccines

“…However, the sudden ZIKV outbreak in South America alerted health authorities and the public to develop a vaccine. Preclinical studies have demonstrated a protective role of CD8 T cells and antibodies against ZIKV infection, the latter being sufficient for complete protection [67][68][69][70]. However, cocirculation of DENV, WNV and ZIKV has been reported in several countries and previous studies suggested an immunological cross-reactivity between viruses, which may drive immune-mediated enhancement [71][72][73].…”

“…Preclinical studies demonstrated that both vaccines induced high neutralising antibody titers and completely protected animals against ZIKV challenges [67,68,75].…”

“…Recombinant protein, DNA and RNA Two DNA based vaccines expressing the ZIKV proteins prM and E are currently tested in healthy volunteers [67,75]. Preclinical studies demonstrated that both vaccines induced high neutralising antibody titers and completely protected animals against ZIKV challenges [67,68,75].…”

“…ZPIV was tested in preclinical studies and demonstrated robust antibody responses against ZIKV in mice and rhesus macaques as well as completely protected animals against ZIKV challenges [67,68].…”