U19AI168632

Early Life Respiratory Viral Infections Shape Immune Development Trajectories - Abstract

Viral respiratory infections are responsible for major morbidity and mortality in early life. Infants account for a significant proportion of influenza hospitalizations and are considered a top high-risk group. In addition to the acute morbidity, initial immune responses to influenza shape/imprint the immune system and affect subsequent responses to influenza infections and vaccinations, which tend to induce humoral responses skewed towards epitopes present in the first influenza antigen encountered.

In contrast, SARS-CoV-2 infection in infants is generally mild and less severe than in older individuals. This is remarkable and suggests that there are unique features on how the infant immune system responds to SARS-CoV-2, compared to its responses against other respiratory viruses, that can be leveraged to improve our understanding of early life immunity.

On the basis of these observations, we hypothesize that early life viral respiratory infections elicit virus-specific immune responses that lead to distinct immune developmental trajectories. To address this hypothesis, we will compare three longitudinal cohorts:

I) Infants infected with SARS-CoV-2;
II) Infants infected with influenza virus; and
III) Healthy infants with none of those two infections.

After acute infection, children will be followed longitudinally for three years and immune responses assessed in the context of influenza and COVID-19 vaccinations.

We designed two integrated research projects, supported by three cores.

Project 1 will define:
1) The differences of blood transcriptional immune signatures in infants with SARS-CoV-2 versus infants with influenza infection;
2) The magnitude, immunodominance pattern, and breadth of the antibody responses to influenza virus and evolution of antibody responses to SARS-CoV-2; and
3) Perform high-throughput longitudinal evaluation of B cell responses to influenza and SARS-CoV-2.

Project 2 will:
1) Assess the blood cell composition, transcriptome, and epigenome in response to influenza and SARS-CoV-2 infection occurring in the first six months of life at the single-cell level; and
2) Characterize the PBMC phenotype/cell composition, transcriptome, and epigenome in response to vaccination against influenza and SARS-CoV-2.

St. Jude Children's Research Hospital

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]

Memphis, Tennessee 38105 United States

Single Zip Code

Immune Development in Early Life (IDEaL) (U19 Clinical Trial Not Allowed) (RFA-AI-20-078)

Amendment Since initial award the total obligations have increased 304% from $1,689,999 to $6,832,917.