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

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

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 370% from $854,272 to $4,014,793.