Study shows key role for human T cells in the control of Respiratory
Syncytial Virus (RSV) infection

Date:
May 24, 2023
Source:
University of North Carolina Health Care
Summary:
A new study has shown that human T cells have an important role
to play in controlling infection.


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FULL STORY ========================================================================== Respiratory Syncytial Virus (RSV) is a highly contagious and seasonal respiratory virus that mainly causes common cold symptoms in healthy
adults but can cause more serious lung infections in infants, the immunocompromised and older individuals. Strikingly, RSV infection remains
the most common reason for hospitalization of infants and young children.

Recently, health officials anticipating a season of respiratory illness to rival some of the worst cold and flu seasons on record, have encouraged
flu shots and reformulated COVID boosters. However, these options
are not currently available for protection against RSV related lung
disease. But this is changing, and a new study published in JCI Insight,
led by Angela Wahl, PhD, Raymond Pickles, PhD, and J. Victor Garcia,
PhD, with the International Center for the Advancement of Translational
Science (ICATS), the Department of Microbiology and Immunology, and the Institute for Global Health and Infectious Diseases (IGHID) at the UNC
School of Medicine has shown that human T cells have an important role
to play in controlling infection.

"Vaccine strategies for RSV have largely focused on the induction of an antibody response. Using novel precision animal models of RSV infection,
we've gained novel insight into how the human immune system, and in
particular human T cells, controls and clears RSV infection," said Wahl, assistant professor of medicine and assistant director of the UNC ICATS.

"Our data shows that T cells can independently control RSV infection
in human lung tissue in the absence of an RSV-specific antibody
response. While a vaccine-induced RSV-specific T cell response would
not be able to prevent infection, it could accelerate virus clearance
and ameliorate disease if vaccine elicited antibodies fail to prevent infection, due to antigenic variability among circulating strains."
The research team used two novel precision animal models to analyze
RSV-induced human lung pathology and human immune correlates of protection
at pre- determined time points. They showed that primed humanCD8+
T cells or CD4+ T cells effectively and independently controlled RSV replication in human lung tissue in the absence of an RSV-specific
antibody response. This preclinical data supports the development of
RSV vaccines which also elicit effective T cell responses to improve
RSV vaccine efficacy.

"It remains to be determined if vaccine efficacy fluctuates during
RSV seasons due to variations in the circulating strains, and how long protection would last. But vaccines which can elicit T cell immunity
may provide long-term protection against RSV infection and limit the
severity of subsequent lung disease" said J. Victor Garcia, professor
of medicine and director of UNC ICATS.

"With our recent experience with a global pandemic caused by SARS-CoV-2
and the success of vaccines which are formulated to elicit neutralizing antibody responses it will be critical to understand how vaccine design
can be tuned to also mount an effective T cell response against viral
pathogens including RSV to more effectively clear infection from the lung"
said Raymond Pickles of the UNC Microbiology and Immunology Department
who was also involved in this study.

An effective and safe RSV vaccine is a priority for the WHO Initiative
for Vaccine Research, but the incomplete understanding of how the human
immune response controls RSV infection has proven to be a major hurdle
towards developing an effective vaccine. On May 3, the U.S. Food and
Drug Administration approved GSK's Arexvy vaccine for the prevention of
lower respiratory tract disease caused by RSV in individuals 60 years
of age and older. Pfizer and Moderna also have two candidate vaccines
that have shown efficacy against RSV-associated respiratory tract in
Phase III clinical trials.

Other investigators include Frederic B. Askin, MD, (Pathology and Lab
Medicine) and Jason K. Whitmire, PhD (Genetics) from UNC, and Guido
Silvestri, MD, from Emory University.

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========================================================================== Story Source: Materials provided by
University_of_North_Carolina_Health_Care. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Chandrav De, Raymond J. Pickles, Wenbo Yao, Baolin Liao, Allison E.

Boone, Mingyu Choi, Diana M. Battaglia, Frederic B. Askin, Jason K.

Whitmire, Guido Silvestri, J. Victor Garcia, Angela Wahl. Human T
cells efficiently control RSV infection. JCI Insight, 2023; DOI:
10.1172/ jci.insight.168110 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230524181935.htm

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