Common cold or COVID-19? Some T cells are ready to combat both – EurekAlert

image:

LJI Research Instructor Annie Elong Ngono (left) and LJI Postdoctoral Fellow Rbens Alves, Ph.D., served as co-first authors of the new SARS-CoV-2 study.

Credit: Matthew Ellenbogen, LJI Creative Producer

Scientistsat La Jolla Institute for Immunology (LJI) have found direct evidence that exposure to common cold coronaviruses can train T cells to fight SARS-CoV-2. In fact, prior exposure to a common cold coronavirus appears to partially protect mice from lung damage during a subsequent SARS-CoV-2 infection.

The new research,published recently inNature Communications, provides an important first look at how "cross-reactive" T cellswhich can fight multiple viruses from the same familydevelop in an animal model. "We are learning how these immune cells develop and function," says study co-leader LJI Research Instructor Annie Elong Ngono, Ph.D.

The Shresta Laboratoryis now working to develop novel vaccines purposefully designed to harness these powerful T cells. Those vaccines would protect against SARS-CoV-2 and provide immunity against several other coronaviruses with pandemic potential.

"Our research willhelp scientists design and improve 'pan-coronavirus' vaccines that elicit broad, cross-protective responses," adds LJI ProfessorSujan Shresta, Ph.D., study senior leader and member ofLJI's Center for Vaccine Innovation.

How powerful areT cells?

T cells tendto be specialists. They learn to hunt down specific molecular targets, called epitopes, that belong to specific pathogens. "Cross-reactive" T cells are important for human health because they recognize epitope targets on differentbut closely relatedpathogens, such as different members of the coronavirus family. This viral family includes common cold coronaviruses and serious pathogens such as SARS-CoV-2.

The COVID-19 pandemicput cross-reactive T cells in the spotlight.In early 2020, LJI ProfessorsShane Crotty, Ph.D., andAlessandro Sette, Dr.Biol.Sci., discovered that many peoplewho had never been exposed to SARS-CoV-2already had T cells that recognized the novel coronavirus. How did these T cells know what to look for?

SARS-CoV-2 only emergedin 2019, but many people had contracted common cold coronaviruses long before then. LJI scientists showed that cross-reactive T cells could recognize targets on both viruses. In follow-up studies, researchers even found an association between cross-reactive T cells and a lower risk of developing severe COVID-19.

If T cellscould learn to target both viruses at once, perhaps scientists could design a vaccine against many types of coronaviruses, including new SARS-CoV-2 variants. That was the hopebut there was still a lot to learn.

"To design bettervaccines we need to know exactly how these protective T cells develop and how long that window of protection lasts," says LJI Postdoctoral Fellow Rbens Alves, Ph.D., who served as first author of the new study.

The Shresta Labis working to answer those questions. The lab members specialize in developing humanized mouse models, which allows them to study infectious diseases and human-relevant immune cell responses in a controlled environment.

Cross-reactive T cellsto the rescue

For the newstudy, the researchers used mouse strains that can produce the exact same variety of T cells as the ones found in humans. The researchers infected these mice with one of the most widespread common cold coronaviruses, called OC43. SARS-CoV-2 and OC43 are both betacoronaviruses.

The scientists foundthat mice infected with OC43 produced CD4+ "helper" T cells and CD8+ "killer" T cells that cross-reacted with SARS-CoV-2. Those cells targeted the same epitopes as T cells collected from humans with SARS-CoV-2 exposure.

Next, the researchersdeveloped a model of sequential infectionwith OC43 infection followed by SARS-CoV-2 in these humanized mice. They examined whether the cross-reactive T cells actually helped protect the mice from severe COVID-19.

Cross-reactive CD4+ "helper"T cells did indeed help counteract the virus's assault on the respiratory system. Mice with previous OC43 exposure showed lower levels of SARS-CoV-2 infection in their airways and were less likely to develop pneumonia and lung damage. Cross-reactive T cells really did help prevent severe disease.

"Our lab's expertisein mouse models has allowed us to go deeper into what human studies have suggested," says Elong Ngono.

Next steps forvaccine design

SARS-CoV-2 is notthe first coronavirus to cause a deadly outbreak. SARS, which caused a deadly outbreak in 2003, was also a coronavirus. So is MERS. This new study is an important step in understanding how T cells might learn to recognize and cross-react to many coronaviruses at onceincluding emerging SARS-CoV-2 variants and other family members with pandemic potential.

Going forward, theteam would like to investigate how exposure to other kinds of common cold coronaviruses affects T cells. Will cross-reactive T cells still develop? Would they seek the same shared epitopes or different targets?

"We now havethe mouse model to study different human infection scenarios, such as the common situation when a person has been infected many times by different common cold coronaviruses before encountering SARS-CoV-2," says Shresta. "We even have a model now to characterize different SARS-CoV-2 vaccine-elicited human relevant T cell responses and determine the contribution of these T cells to the vaccine-induced protection."

Shresta says theInstitute is well equipped to move forward with this pandemic prevention research. She credits the LJI for making sure LJI scientists have the vital training and facilities for infectious disease research. Shresta also emphasizes that philanthropic support made it possible for the Institute to construct a biosafety level 3 laboratory for thisand many othercritical studies.

Additional authors ofthe study, "Common cold coronavirus-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," include Julia Timis, Robyn Miller, Kristen Valentine, Paolla Beatriz Almeida Pinto, Andrew Gonzalez, Jose Angel Regla-Nava, Erin Maule, Michael N Nguyen, Norazizah Shafee, Sara Landeras Bueno, Eduardo Olmedillas, Brett Laffey, Katarzyna Dobaczewska, Zbigniew Mikulski, Sara McArdle, Sarah R. Leist, Kenneth Kim, Ralph S. Baric, and Erica Ollmann Saphire.

This research wassupported by the National Institutes of Health (grants U19 AI142790, U01 AI151810, and AI149644), the Overton family, and the Arvin Gottlieb Foundation.

DOI:10.1038/s41467-024-45043-2

About La JollaInstitute

La Jolla Institutefor Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease. Visitlji.orgfor more information.

Nature Communications

Experimental study

Animals

"Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice"

26-Jan-2024

The authors declare no competing interests.

See original here:

Common cold or COVID-19? Some T cells are ready to combat both - EurekAlert