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