LA JOLLA — One experimental vaccine used Zika virus outer coat proteins as they occur in nature, while the second experimental vaccine used Zika virus outer coat proteins with a mutated fusion loop. The unmodified vaccine prompted the immune system to fight Zika virus infection with both antibodies and T cells. Transferring CD8+ T cells from mice vaccinated with the unmodified vaccine into unvaccinated animals reduced Zika virus levels.

The fusion loop is the site on the virus that generates most of the cross-reactive antibodies behind antibody-dependent enhancement. Antibody-dependent enhancement occurs when antibodies bind a virus without disabling it, potentially ferrying the virus into immune cells and driving a more severe infection. The envelope proteins of Zika virus and dengue virus are similar enough that antibodies raised against one routinely bind to the other.

The antibodies from the fusion-loop mutant vaccine did not protect unvaccinated animals. Removing CD8+ T cells eliminated the protection provided by the fusion-loop mutant vaccine. "This vaccine wasn't protecting via antibodies," Shresta said. "It was protecting via T cells." "The protection came from CD8+ T cells, a type of immune cell that finds and destroys virus-infected cells." Twelve weeks after the final dose, mice given the fusion-loop mutant vaccine were no better protected than unvaccinated animals. In contrast, twelve weeks after the final dose, mice given the unmodified vaccine were still protected.

Kantinan Chuensirikulchai, a Visiting Scientist at the La Jolla Institute for Immunology, explained the cellular mechanism. Twelve weeks after the final dose, mice given the fusion-loop mutant vaccine were no better protected than unvaccinated animals. In contrast, twelve weeks after the final dose, mice given the unmodified vaccine were still protected.

Annie Elong Ngono, a Research Instructor at the La Jolla Institute for Immunology, commented on the direction of future development. "We need innovative vaccines," Ngono said. "And now we know what to focus on." Shresta stated that the long-term goal of the lab is to develop a vaccine that provides long-term protection against all of these viruses.

Why It Matters

Zika virus belongs to the orthoflavivirus family, which also includes dengue virus and Japanese encephalitis virus. T cells can cross-react and respond to several related viruses, such as Zika and dengue, at the same time. Chuensirikulchai said the study shows the importance of considering T cell-mediated immunity alongside neutralizing antibodies.

There are currently no specific treatments or vaccines approved for Zika virus. The virus is carried by different species of Aedes mosquitoes. At least 97 countries and territories have reported evidence of Zika virus transmission, according to the World Health Organization. Reported Zika virus cases have fallen sharply since 2017.

Timeline

The World Health Organization declared the surge in Zika-linked birth defects a "public health emergency of international concern" in February 2016. The World Health Organization's public health emergency of international concern designation for Zika virus lasted until November 2016. Sujan Shresta published a study showing that an experimental Zika virus vaccine can protect mice through T cells alone, without help from antibodies.

What's New

A study published in Science Advances found that CD8(+) T cells mediate protection against Zika virus induced by an NS3-based vaccine. Additional context identifies the La Jolla Institute as a research institute. The World Health Organization is a United Nations agency concerned with international public health.