First live-attenuated Zika vaccine induces protective immunity in mice

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The first live-attenuated Zika vaccine has been demonstrated to induce protective immunity in mice after a single dose, according to a study by the University of Texas Medical Branch at Galveston (TX, USA) and Instituto Evandro Chagas (Belém, Brazil).

Developing an effective vaccine against Zika virus (ZIKV) has been a top priority in order to protect women of childbearing age and prevent the congenital complications associated with Zika. Progress been made in subunit and inactivated vaccines, which have been demonstrated to be effective in mice and nonhuman primates. However, in this study, published recently in Nature Medicine, the team chose to work on a live-attenuated vaccine.

Author Pei-Yong Shi (University of Texas) explained their rationale: “We chose to pursue a vaccine made from live virus that has been sufficiently attenuated or weakened, to be safe, and is able to illicit robust immune response to protect us from ZIKV infection. Such live-attenuated vaccine has the advantage of single-dose immunization, rapid and strong immune response and potentially long-lived protection,”

“A successful vaccine requires a fine balance between efficacy and safety – vaccines made from attenuated live viruses generally offer fast and durable immunity, but sometimes with the trade-off of reduced safety, whereas inactivated and subunit viruses often provide enhanced safety but may require several doses initially and periodic boosters. Therefore, a safe live-attenuated vaccine will be ideal in prevention of ZIKV infection, especially in developing countries.”

The team engineered the Zika virus; deleting a 10-nucleotide segment in the 3′ untranslated region of the ZIKV genome. This approach is similar to the method utilized in a dengue virus vaccine currently in Phase III clinical trials.

The researchers demonstrated the altered virus was highly attenuated, immunogenic, and protective in the mouse model, critically inducing protective immunity after just a single dose. In addition, the team observed the mice also developed a robust T cell response after immunization with this vaccine.

The team hope the vaccine might overcome safety issues often found in live-attenuated vaccines, for example, they demonstrated the engineered ZIKV was incapable of infecting mosquitoes after feeding on spiked-blood meals.

Shi commented: “Safety is a major hurdle when developing a live-attenuated vaccine. Our Zika vaccine showed promising safety profile in mice when compared with clinically approved live-attenuated vaccines, such as the yellow fever vaccine.”

In light of these promising results the researchers hope to further develop this live-attenuated ZIKV vaccine candidate.

Sources: Shan C, Muruato AE, Nunes BTD et al. A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nat Med. doi:10.1038/nm.4322 (2017) (Epub ahead of print); www.utmb.edu/newsroom/article11496.aspx

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