Editors' ChoiceInfectious Disease

Defeating Zika

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Science Translational Medicine  26 Apr 2017:
Vol. 9, Issue 387, eaan2785
DOI: 10.1126/scitranslmed.aan2785


A live attenuated Zika virus vaccine produces sterilizing immunity in mice

The Zika virus (ZIKV) epidemic created an urgent need for vaccines targeting this devastating virus, and the scientific community quickly responded to the challenge. In just one year, several promising inactivated virus and nucleic acid-based vaccines have yielded encouraging results in animal models, especially in terms of the vaccines’ ability to produce a neutralizing antibody response. But for related neurotropic flaviviruses including West Nile virus and Japanese encephalitis virus, CD8+ T cell responses also play a crucial role in clearing infection from the central nervous system (CNS), and the same is also likely to be true for ZIKV.

A live attenuated vaccine (LAV) has the advantage of displaying epitopes in a way that resembles a natural ZIKV particle. A LAV also encodes nonstructural proteins, which provide additional T cell epitopes as well as important targets for the humoral immune response. Using a strategy employed in the development of vaccines against dengue virus (DENV), Shan et al. generated a LAV against ZIKV by deleting 10 nucleotides from the 3′ untranslated region of the ZIKV genome. They tested the vaccine in knockout mice lacking the type I interferon (IFN) receptor (A129 mice), since these mice are highly susceptible to neuroinvasive infection with ZIKV and frequently develop encephalitis, paralysis, seizures, and death. Remarkably, the authors found that inoculation with just 10 infectious particles of the LAV was sufficient to induce sterilizing immunity, including neutralizing antibodies and a potent CD8+ T cell response.

However, when it comes to generation of a safe vaccine against ZIKV, there are additional hurdles to consider, including whether a vaccine is safe in pregnancy. Furthermore, cross-reactive antibodies among various strains of DENV produce antibody-dependent enhancement (ADE), which can trigger life-threatening dengue hemorrhagic fever. ADE between ZIKV and DENV has already been demonstrated in animal models, and more study is required to determine whether clinically relevant ADE occurs between ZIKV and DENV, since this would have major implications for the safety profile of any potential ZIKV vaccine in humans.

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