R01AI161008

Early Life B Cell Responses and Inflammation Following SARS-CoV-2 Infection

Abstract

As of March 2021, SARS-CoV-2 has caused more than 50 million infections and 2 million deaths, constituting an unprecedented pandemic in the modern world. While infected individuals rapidly develop IgG responses against the viral spike after infection, some studies have indicated that individuals with mild infection generate weaker neutralizing antibody (Ab) responses compared to those with severe disease. The durability of the immune response following natural infection and its afforded protection against subsequent infections and emerging related variants remain unclear.

Interestingly, unlike other respiratory viruses, children rarely develop severe disease following SARS-CoV-2 infection. Antibody responses in hospitalized children and those who developed the multisystem inflammatory syndrome (MIS-C) have been characterized. However, there is a gap in knowledge regarding the magnitude, quality, durability, and breadth of antibody responses in asymptomatic or mildly symptomatic children. These responses may contribute to making children less susceptible to severe infection compared to adults. Moreover, the possibility of reinfection or infection with a novel variant in previously-infected children is not known, making the possibility of restarting congregate settings for children without a childhood vaccine quite challenging.

Our overarching goal is to characterize the kinetics, function, breadth, and durability of humoral immune responses elicited by SARS-CoV-2 infection across the pediatric age spectrum in comparison to that of adults. We hypothesize that pediatric immune responses to SARS-CoV-2 infection are distinct from that of adults and associate with protection against symptomatic disease and durability of immunity.

Using samples from two unique ongoing community studies of SARS-CoV-2 infections in adults and children, we will test our hypothesis through the following aims:

1) Define the similarities and differences in the kinetics, magnitude, specificity, function, and durability of SARS-CoV-2-specific antibody responses in children and adults.
2) Investigate the breadth and potency of antibody responses in SARS-CoV-2-infected children against established and predicted variants of SARS-CoV-2.
3) Define the SARS-CoV-2-specific B cell repertoire and characterize the potency of pediatric SARS-CoV-2-specific monoclonal antibodies.

These evaluations will identify immune correlates of protection against severe disease and provide insights for immunization strategies towards the long-term control of SARS-CoV-2, which will likely become an endemic pathogen.

Weill Medical College Of Cornell University

NOT APPLICABLE

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

New York, New York 100654805 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 272% from $854,272 to $3,176,340.