Where Aedes mosquitoes fly, the Zika virus may not be far away. Although the explosive 2015-2016 Zika epidemics in America are behind us, Zika may reappear and “in many countries Zika may be spreading in silence,” says Dr. Sujan Shresta, professor at the La Jolla Institute of Immunology (LJI). “We need to develop effective vaccines.”
In a new Science Advances study, Shresta and her colleagues at LJI report that the T cells of the immune system have the ability to prevent Zika infection in mice. This finding suggests that effective Zika vaccines must activate T cells in order to work with antibodies.
“When we combine T cells and antibodies, we have even stronger protection and longer-term protection,” says Annie Elong Ngono, Ph.D., postdoctoral fellow at LJI and first author of the new study.
Zika virus cases are usually mild, but the virus can cause serious congenital birth defects in infants and neurological complications in adults and children.
Since Zika hit the headlines in 2016 when cases of the virus peaked in America, researchers have developed more than 40 Zika vaccine candidates. The vast majority of these vaccines are designed to induce the body to make antibodies that target a specific protein in the virus.
Unfortunately, there is a disadvantage to this neutralizing antibody approach. In many parts of the world, Zika virus is spreading alongside related mosquito-borne viruses such as dengue fever. Scientists have found that the presence of anti-Zika antibodies can make a later case of dengue fever much, much worse.
In a 2018 study, Shresta’s lab showed that newborn mouse pups that contained anti-Zika antibodies were more prone to death from dengue exposure than mice that lacked anti-Zika antibodies.
In theory, similar cases of “antibody dependent enhancement” can lead to cases where residual anti-Zika antibodies in a patient facilitate dengue invasion of host cells – which is particularly devastating in pregnant patients.
This means that a Zika vaccine that only prompts for antibody production can be risky in areas where both dengue and Zika are common. Fortunately, the immune system can do more than just make antibodies.
For the new study, Shresta and Elong Ngono tested an experimental Zika vaccine in a mouse model. The vaccine is designed to create the arm of the immune system that makes up T cells. The mice received the vaccine, received a second shot four weeks later, and were exposed to Zika six weeks later.
The team found that the vaccine can induce strong immunity to a potentially fatal Zika virus infection by primarily inducing CD8 + T cells, also known as “killer” T cells, against the virus. The vaccine also prevented transmission of Zika across the placenta from mother to fetus in pregnant mice.
This vaccination approach was even more effective when combined with a vaccine candidate that induced neutralizing antibodies. “We found that having a vaccine that induces both T cells and antibodies is better than one on its own,” says Elong Ngono.
The new research also shows the importance of targeting more than one viral protein when fighting flaviviruses, the group of viruses including Zika, dengue, yellow fever, and Japanese encephalitis. By getting T cells and antibodies to recognize key sites on these related viruses, researchers may be closer to developing a “pan-flavivirus” vaccine to protect people in areas where several of these diseases are common.
“We believe this approach can be used against other infectious diseases,” says Elong Ngono. For example, recent research by LJI scientists suggests that COVID-19 vaccines may also need to trigger T cells in order to work alongside antibodies.
The challenge now is to figure out how to best elicit balanced antibody and T cell responses. We also don’t know how durable the vaccination protection is – if it’s pretty short, let’s see how we can improve it. “
Sujan Shresta, Ph.D., Professor at the La Jolla Institute of Immunology
La Jolla Institute of Immunology