T cells are a powerful force against Zika virus

LJI scientists tested two Zika vaccines, both designed to work through antibodies. One protected through T cells instead—but only the vaccine that mustered both held off the virus for the long haul.

La Jolla Institute for Immunology

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La Jolla Institute for Immunology (LJI) Professor Sujan Shresta, Ph.D., studies how the immune system targets Zika virus infection. Her lab has found that a vaccine approach could activate T cells to help protect the human body from severe Zika virus infection.

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Credit: La Jolla Institute for Immunology

LA JOLLA, CA—Zika virus has been spreading for decades, but it first grabbed worldwide headlines in 2016. That February, with an outbreak sweeping the Americas, the World Health Organization (WHO) declared the surge in Zika-linked birth defects a “public health emergency of international concern”—a designation which lasted until that November. An estimated one million people or more were infected before the wave subsided.

Zika virus is carried by different species of Aedes mosquitoes. These mosquitoes had spread into new regions and found new victims. More people were getting sick, including pregnant women.

Doctors realized that the increased cases of microcephaly (significantly smaller brain and head development) in newborns across the Americas were caused by Zika virus infection. Women who contracted Zika virus during pregnancy were also much more likely to miscarry. Babies who survived could be born with eye and ear problems and joint issues, a pattern of birth defects doctors now group together as congenital Zika syndrome.

Today, at least 97 countries and territories have reported evidence of Zika virus transmission, according to the WHO. Reported cases have fallen sharply since 2017, but researchers expect the pool of susceptible people to rebuild over the coming decade, and a warming climate and the spread of insecticide-resistant Aedes mosquitoes keep widening the map of who is at risk. We still do not have any specific Zika virus treatments or vaccines.

Researchers at La Jolla Institute for Immunology (LJI) aim to change that by investigating how we can design vaccines that provide long-lasting, effective protection against severe Zika virus infection.

LJI Professor Sujan Shresta, Ph.D., recently published a study in Nature Microbiology showing that an experimental Zika virus vaccine can protect mice through T cells alone, without help from virus-fighting antibodies. The catch: on their own, those T cells do not keep the protection going.

This discovery is a critical step in the fight against Zika virus and its close viral relatives, including the life-threatening dengue virus. “The long-term goal of our lab is to develop a vaccine that provides long-term protection against all of these viruses,” says Shresta.

Why don’t we have Zika virus vaccines?

Most vaccines work by prompting the body to make antibodies, which bind to part of a pathogen—the outside of a virus, say—and neutralize it before it can cause infection. Antibodies and the B cells that produce them can then linger in the blood for years, lying in wait for their targets.

But in the case of Zika virus vaccines, antibodies pose a big problem. Zika belongs to a family of mosquito-borne viruses—the orthoflaviviruses—that also includes dengue and Japanese encephalitis virus, and these viruses overlap across much of the world. Zika and dengue are especially close cousins: the envelope proteins that coat them are so similar that antibodies raised against one routinely latch onto the other.

Shresta has studied a phenomenon called antibody-dependent enhancement (ADE). When antibodies bind a virus without disabling it—because they were raised against a relative, or because their levels have waned—they can end up ferrying the virus into immune cells instead of blocking it, driving a more severe infection. Because of ADE, a person who receives a vaccine that prompts the body to make antibodies against Zika virus could be vulnerable to a severe case of Zika or dengue infection later on.

The risk of ADE means vaccine researchers need to find innovative ways of protecting the body from orthoflaviviruses.

In past studies, Shresta uncovered the potential power of T cells in fighting orthoflaviviruses. T cells patrol the body for signs of disease and adapt over time to recognize specific threats, and vaccines can train them just as they train antibodies. Shresta has shown that T cells offer a chance to fight these viruses when you can’t depend on antibodies.

Vaccine yields surprising results

For the new study, Shresta worked with LJI Research Instructor Annie Elong Ngono, Ph.D., and Visiting Scientist Kantinan Chuensirikulchai, Ph.D., to compare two experimental Zika vaccines in mice bred to be susceptible to the virus. 

Like most Zika vaccine candidates, both were built around the virus’s outer coat proteins to elicit neutralizing antibodies. In one, those proteins were left as they occur in nature. In the other, the team mutated a small patch called the fusion loop, the very site that generates most of the cross-reactive antibodies behind ADE. The researchers wanted to know whether removing that liability would also change how T cells respond.

In their tests, the unmodified vaccine got the immune system to fight Zika virus infection with a double-whammy of antibodies and T cells. Transferring CD8+ T cells from those mice into unvaccinated animals cut Zika levels on its own—so T cells were pulling real weight even in the vaccine whose antibodies worked as intended.

The fusion-loop mutant vaccine came with an even bigger surprise. Its antibodies shared many features in cell cultures and test tubes as those from the unmodified vaccine, but they did not protect unvaccinated animals at all. Stripping out the CD8+ T cells, by contrast, wiped the protection away. “This vaccine wasn’t protecting via antibodies,” says Shresta. “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,” adds Chuensirikulchai.

This protection was effective, but it didn’t last. Twelve weeks after the final dose, mice given the fusion-loop mutant vaccine were no better off than unvaccinated animals, while those given the unmodified vaccine were still protected. The lesson is a cautionary one: a change made to reduce ADE risk quietly cost the vaccine its staying power. 

Shresta and her colleagues are now investigating how to build up a “durable” army of T cells that can respond to Zika virus infection for years after vaccination. “We need innovative vaccines,” says Elong Ngono. “And now we know what to focus on.”

What’s next for life-saving vaccines?

This work doesn’t stop with a Zika virus vaccine, says Shresta. She has found that T cells have the power to “cross-react” and respond to several related viruses, such as Zika and dengue, at the same time.

The new study brings Shresta’s team closer to a “pan-orthoflavivirus vaccine” that could teach T cells to fight many of these viruses at once—an approach that would be worth a great deal in the many places where people meet more than one related virus.

As Chuensirikulchai explains, the new findings reinforce the idea that effective vaccines against orthoflaviviruses should prompt the body to make virus-specific and cross-reactive T cells in addition to antibodies that neutralize and avoid ADE.

“Our study highlights the importance of considering T cell-mediated immunity alongside neutralizing antibodies,” says Chuensirikulchai. “This concept may inspire new vaccine strategies for other orthoflaviviruses, particularly in situations where antibody responses alone are insufficient or may contribute to unwanted immune effects.”

Publication details:

Additional authors of the study, "A Zika Virus Vaccine with E Protein Fusion Loop Mutations Protects via CD8+ T Cells,” are Qin Hui Li, Hsueh-han Lu, Julia Timis, Manuel Montano, Luke Eder, Pradip Bhandari, Dawid Zyla, Maximilian Bunz, Henry Madany, Rubens Alves, Paolla Beatriz Almeida Pinto, Erin Maule, Michael Nguyen, Erica Ollmann Saphire, and Lakshmanane Premkumar.

This study was supported by the National Institutes of Health (grants R01AI153500, R01AI163188, R01AI180196, and U19AI181960) and the Prebys Foundation Research Heroes program.

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Journal

Nature Microbiology

DOI

10.1038/s41564-026-02465-6 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

A Zika virus vaccine with E protein fusion loop mutations protects via CD8+ T cells

Article Publication Date

26-Aug-2026

 

People say they would not want to test embryos for traits like low IQ. But if given the information, they act on it

University of Oxford

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Available for use with credit to Awad et al., Nature Human Behaviour (2026).

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Credit: Awad et al., Nature Human Behaviour (2026).

A study of more than 2,000 people in the United States and China finds that the line between medical and non-medical traits, which underpins the rules on embryo testing in most countries, does not match the preferences of the public .

If undertaking artificial fertility treatment, most people say they are more comfortable testing embryos for a disease than for a trait like low IQ or antisocial behaviour. But when they are shown that information and asked to pick an embryo, the distinction largely disappears. They decide not to implant  embryos with a raised chance of low IQ or antisocial behaviour about as often as they decide not to implant embryos with a raised chance of heart disease.

That is the finding of a study published today in Nature Human Behaviour by researchers at the University of Oxford, the University of Exeter, the Yong Loo Lin School of Medicine, National University of Singapore (NUS), and colleagues in the UK, Canada, China and Australia.

IVF clinics and commercial companies now offer polygenic testing of embryos, which estimates an embryo's chances of developing common conditions such as heart disease or diabetes, and in some cases traits such as height, eye colour or cognitive ability. Most countries have rules that draw  a distinction between medical and non-medical uses of embryo selection. Earlier surveys supported that line, finding strong public backing for testing for serious illness and much weaker backing for testing for traits.

The new study separated two things those surveys ran together: whether people want the information, and what they do if they have it.

In a US sample of 1,467 adults, quota-sampled to match the national population, 735 people were asked whether they would test embryos for four attributes. Willingness to test was highest for heart disease at 79 per cent and lowest for vision impairment at 55 per cent, with low IQ at 65 per cent and antisocial behaviour at 58 per cent in between. On average, people were more willing to test for the two medical conditions than for the two non-medical traits.

The other 732 people were instead given information about the genetic properties of pairs of embryos and asked to choose between them. Here the pattern changed. An embryo with an above-average chance of heart disease was 40 percentage points less likely to be picked (compared with one with an average chance). For antisocial behaviour the gap was 36 points and for low IQ 32 points. For vision impairment, a medical condition, it was 19 points, far below both non-medical traits.

The same study run with 623 adults in China produced the same shape of result, with the gaps slightly larger.

Dr Edmond Awad of the University of Exeter and the Uehiro Oxford Institute, who led the study, said:

"People are uneasy about asking for this kind of information, but they act on it once it is in front of them. Psychologists call that deliberate ignorance. Choosing not to look is not the same as not caring."

Professor Julian Savulescu of NUS Medicine and the University of Oxford, the study's senior author, said: 

"Regulation in this area rests on a category. Our results suggest people do not think in categories when the choice is in front of them. If policy is going to track what matters to people, it will have to talk about the effect a condition or trait has on a child's life, not the label attached to it."

Professor Dominic Wilkinson, a neonatologist at the John Radcliffe Hospital and a corresponding author of the study, said: 

"This study has important implications  for consent for genetic testing in fertility treatment. When deciding whether to undertake testing, prospective parents may find it helpful to reflect not on what they wish to know, but instead, on what information would impact their decisions about embryos.. " 

The authors are careful about what the study does and does not show. It measures what people say they would do in hypothetical scenarios, not what they do in a clinic. It covers four attributes, chosen as test cases, rather than the full range of things a test might report. And the scenarios presented every attribute in the same clean format, which flatters the science: polygenic prediction for behavioural traits such as cognitive ability is far weaker within families than these scenarios imply, so the real-world gains from selecting on them would be much smaller.

The study also found that public willingness to test for non-medical traits was higher than earlier work had suggested, with 61 per cent open to it. The authors note that their questions asked about avoiding low IQ and antisocial behaviour, whereas earlier studies asked about selecting for high IQ and prosocial behaviour, and that the difference in wording may account for much of the gap.

The team is now running a larger version of the question through Tinker Tots (https://tinker-tots.net), an online citizen-science platform, which invites the public to work through embryo selection dilemmas across a wider range of traits and in more countries. The study published today used a separate sample recruited through Prolific.

 

Notes to editors

Paper: Awad, E., Colombatto, C., Demaree-Cotton, J., Earp, B. D., Everett, J. A. C., Liu, P., Schaefer, G. O., Singh, I., Wilkinson, D., & Savulescu, J. "Public perceptions of polygenic testing and embryo selection for non-medical traits." Nature Human Behaviour (2026). DOI: 10.1038/s41562-026-02562-w

Available from 26 August at: https://www.nature.com/articles/s41562-026-02562-w

Registered Report. The study design, hypotheses and analysis plan were reviewed and accepted by the journal before the data were collected, on 7 October 2025. The results could not be shaped after the fact. Two of the seven preregistered hypotheses were not supported, and both are reported.

Data, code and materials: https://osf.io/vb9c2

Ethics: Approved by the Social Sciences and Humanities Interdivisional Research Ethics Committee, University of Oxford (R80692), and the Research Ethics Board of the Center for Psychological Sciences, Zhejiang University (2025-002).

Funding: This research was funded in part by the Wellcome Trust (grant number: 226801) for Discovery Research Platform for Transformative Inclusivity in Ethics and Humanities Research (ANTITHESES). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This research was also supported by the National University of Singapore under J.S.’s NUS Start-Up grant (NUHSRO/2022/078/Startup/13). It was also supported by the Social Science Research Council (Singapore) and administered by the Ministry of Education, Singapore, under its Social Sciences Research Thematic Grant (SSRC2023-SSRTG-006). This research was also supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (NIHR203316). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Study 1b was supported by P.L.'s Start-up Fund for 'Hundred Talents Program' of Zhejiang University. B.D.E. was supported by NUSMed and ODPRT (NUHSRO/2024/035/Startup/04) for the project 'Experimental Philosophical Bioethics and Relational Moral Psychology'. J.A.C.E. was supported through a Philip Leverhulme Prize (PLP-2021-095). J.S. was further supported through the Murdoch Children's Research Institute by the Victorian State Government's Operational Infrastructure Support (OIS) Program. None of the funders had any role in study design, data collection and analysis, decision to publish or preparation of the article.

Media contacts:

[Edmond Awad, e.awad@exeter.ac.uk]

[Julian Savulescu, jsavules@nus.edu.sg]

[Dominic Wilkinson, dominic.wilkinson@uehiro.ox.ac.uk]

 

Interviews available: Edmond Awad (Exeter and Oxford, UK), Julian Savulescu (NUS, Singapore and Oxford, UK).

 

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Journal

Nature Human Behaviour

DOI

10.1038/s41562-026-02562-w 

Method of Research

Survey

Subject of Research

People

Article Title

Public perceptions of polygenic testing and embryo selection for non-medical traits.

Article Publication Date

26-Aug-2026

COI Statement

This research was funded in part by the Wellcome Trust (grant number: 226801) for Discovery Research Platform for Transformative Inclusivity in Ethics and Humanities Research (ANTITHESES). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This research was also supported by the National University of Singapore under J.S.’s NUS Start-Up grant (NUHSRO/2022/078/Startup/13). It was also supported by the Social Science Research Council (Singapore) and administered by the Ministry of Education, Singapore, under its Social Sciences Research Thematic Grant (SSRC2023-SSRTG-006). This research was also supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (NIHR203316). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Study 1b was supported by P.L.'s Start-up Fund for 'Hundred Talents Program' of Zhejiang University. B.D.E. was supported by NUSMed and ODPRT (NUHSRO/2024/035/Startup/04) for the project 'Experimental Philosophical Bioethics and Relational Moral Psychology'. J.A.C.E. was supported through a Philip Leverhulme Prize (PLP-2021-095). J.S. was further supported through the Murdoch Children's Research Institute by the Victorian State Government's Operational Infrastructure Support (OIS) Program. None of the funders had any role in study design, data collection and analysis, decision to publish or preparation of the article.

 AFRICA

Improved maternity care linked to fewer deaths

Karolinska Institutet

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Claudia Hanson

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Credit: Photo: Ulf Sirborn

A combination of training, quality improvement and leadership support in hospitals across four countries in sub-Saharan Africa is linked to fewer stillbirths and deaths among newborns during the first 24 hours of life. This is shown by a study led by Karolinska Institutet and published in Nature Medicine.

Despite major advances in maternal and child healthcare, the risk of a child dying during labour or shortly after birth remains very high in several countries in sub-Saharan Africa. To improve care during labour, researchers within the ALERT project developed an intervention combining several different elements.

The work began with a process known as co-design, in which women, families and healthcare staff jointly identified needs and barriers in care. Based on this, training programmes were developed for midwives and other maternity staff. Hospitals also received support for their quality improvement work, and managers in the maternity wards were offered mentoring.

The study was carried out at 16 maternity units in Benin, Malawi, Tanzania and Uganda. A total of 134,630 women and 139,300 newborns were included. To monitor the results, the researchers set up a digital perinatal register based on the birth registers used in countries such as Sweden. The register was used both for research and to provide feedback to healthcare staff during the course of the project.

The results show that the chance of early perinatal death, defined as stillbirth or death within the first 24 hours of life, fell by 22 per cent following the introduction of the ALERT programme. The researchers also observed a 19 per cent reduction in oxygen-deprivation-related complications among newborns.

Sub-Saharan Africa is the region of the world where the highest number of babies are stillborn. Around one million children show no signs of life at birth every year, and the risk of a child dying during childbirth is around 40 times higher than in Europe.

The loss of a child often causes great suffering for families and can lead to feelings of guilt, shame and social vulnerability, explains Claudia Hanson, professor at the Department of Global Public Health, Karolinska Institutet, and the study’s principal investigator.

”This inequality is unacceptable. Our findings show that it is possible to reduce mortality and morbidity among newborns by improving the quality of maternity care, optimising working practices and strengthening care teams and leadership, even in settings where resources are limited and midwives work under high pressure. The study offers hope and presents a model that can be applied in other places too,” she says.

The researchers also observed that foetal heart rate monitoring improved during the study and that the proportion of caesarean sections increased slightly. According to the researchers, this may indicate that complications were detected earlier and that healthcare staff were more often able to take timely action.

The next step is to investigate how improved monitoring of the foetus during labour can contribute to further improvements.

”We believe that better support for interpreting signs of foetal distress during labour can help to further reduce the still-high mortality rate. We therefore want to develop new approaches, potentially also using AI-supported descion-support systems and improved guidelines in collaboration with healthcare staff,” says Claudia Hanson.

See the study for details of funding bodies and any conflicts of interest.

Publication: “A multi-faceted hospital-based intervention for intrapartum care in Sub-Saharan Africa: a step-wedge, cluster-randomised trial”, Claudia Hanson, Joseph Akuze, Kristi Sidney Annerstedt, Helle Mölsted Alvesson, Sunjuri Sun, Manuela Straneo, Nicola Orsini, Lenka Benova, Mechthild M. Gross, Bruno Marchal, Rian Snijders, Effie Chipeta, Peter Waiswa, Hussein Kidanto, Jean-Paul Dossou, Andrea Barnabas Pembe, Nature Medicine, online August 26, 2026, doi: 10.1038/s41591-026-04599-w

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Journal

Nature Medicine

DOI

10.1038/s41591-026-04599-w 

Subject of Research

People

Article Title

“A multi-faceted hospital-based intervention for intrapartum care in Sub-Saharan Africa: a step-wedge, cluster-randomised trial”

Article Publication Date

26-Aug-2026

Volcanic eruptions and a warming climate have disrupted close connections between the Indian and Pacific oceans

Woods Hole Oceanographic Institution

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Woods Hole, Mass. (August 26, 2026) - A new study that combines paleoclimate data and climate models suggests that large volcanic eruptions can disrupt the relationship between atmospheric circulations of the tropical Indian and Pacific oceans. In addition, human-caused greenhouse gas emissions are now driving an unprecedented breakdown in inter-basin coupling, according to researchers at the Woods Hole Oceanographic Institution (WHOI).

Volcanism can temporarily weaken connections between ocean basins, but anthropogenic forcings in recent decades have caused an “exceptional” shift in the relationship between Indian and Pacific Ocean climate variability, according to a Nature Communications study, “Coupling of Pacific and Indian Ocean variability disrupted by 19th century volcanism.”

Climate conditions in the Indian Ocean typically follow the behavior of the Pacific Ocean. However, since the 1980s, scientists have observed a breakdown of this co-variability linked to climate change. With less than a hundred years of quality instrumental data, it is difficult to assess how unusual these recent changes really are. To provide long term context, WHOI scientists used tropical paleoclimate archives – corals, tree rings, and stalagmites – to extend the record of Indian and Pacific Ocean climate back to the early 1600s.

Consistent with modern observations, the paleo-records show that the two ocean basins were largely coupled for most of the last four hundred years. But a key finding from this study is that the Indian-Pacific relationship appeared notably different during the early 19th century (1810–1850). The researchers link this unusual period to a series of large tropical volcanic eruptions that disrupted the usual connections between the two ocean basins, with computer simulations covering the past millennium supporting this explanation. The extent to which volcanic eruptions weakened Pacific influences on Indian Ocean climate depended on the strength of the eruptions and the climate conditions at the time. “This is one of the first studies to examine the breakdown in the connection between the Pacific and Indian oceans using evidence from past climates, modern observations, and climate models,” said co-author Caroline Ummenhofer, a senior scientist at WHOI.

Showing how volcanic eruptions can weaken the Indian-Pacific relationship is only one outcome; this study helps frame how unprecedented and how exceptional the recent breakdown is.“The modern data we have is [RS1] limited and doesn’t go back far enough. With climate models and paleo-records, we are now able to say with more confidence that the recent changes we are seeing are really quite exceptional,” said lead author Shawn Wang. Wang is a former WHOI graduate student and postdoctoral researcher, and he is currently a postdoc at the University of Colorado Boulder.

Understanding this breakdown is important because connections between ocean basins help scientists predict future changes in rainfall and other aspects of the climate. While previous studies have often focused on individual ocean basins, this study looks at how the oceans influence one another.

“A key finding is that global warming and human emissions are now overwhelming the Pacific’s natural influence on the Indian Ocean,” Ummenhofer said.

“The Indian Ocean is a huge heat reservoir, and it can decouple from what the Pacific Ocean is doing. The results of this study underscore the independent behavior of the Indian Ocean,” said co-author Delia Oppo, an emeritus research scholar at WHOI.

This study was supported by the U.S. National Science Foundation, the WHOI Investment in Science Program, and the WHOI Academic Programs Office.

Authors: Shawn Wang1, Delia Oppo2, and Caroline Ummenhofer3

Affiliations:

1Former graduate student and postdoctoral researcher, Woods Hole Oceanographic Institution, Woods Hole, MA; current postdoc, University of Colorado Boulder

2Emeritus Research Scholar, WHOI

3Senior Scientist, WHOI

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About Woods Hole Oceanographic Institution

The Woods Hole Oceanographic Institution (WHOI) is a private, non-profit organization on Cape Cod, Massachusetts, dedicated to marine research, engineering, and higher education. Established in 1930, its primary mission is to understand the ocean and its interaction with the Earth as a whole, and to communicate an understanding of the ocean’s role in the changing global environment. WHOI’s pioneering discoveries stem from an ideal combination of science and engineering—one that has made it one of the most trusted and technically advanced leaders in basic and applied ocean research and exploration anywhere. WHOI is known for its multidisciplinary approach, superior ship operations, and unparalleled deep-sea robotics capabilities. We play a leading role in ocean observation and operate the most extensive suite of data-gathering platforms in the world. Top scientists, engineers, and students collaborate on more than 800 concurrent projects worldwide—both above and below the waves—pushing the boundaries of knowledge and possibility. For more information, please visit www.whoi.edu

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 [RS1]Suzanne, what is your style preference here: “is” or “are”?

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Journal

Nature Communications

DOI

10.1038/s41467-026-76705-y 

Method of Research

Computational simulation/modeling

Subject of Research

Not applicable

Article Title

Coupling of Pacific and Indian Ocean variability disrupted by 19th century volcanism.

Article Publication Date

26-Aug-2026