R01AI173194

Longitudinal SARS-CoV-2 mRNA vaccine-induced mucosal, serological, and cellular immunity in children and human milk - project summary

COVID-19 cases and hospitalizations in children have increased dramatically worldwide. Although most COVID-19 is mild in children, severe illness and post-infectious complications can occur. We and others have found that children are an important source of household and community transmission. Vaccination is the most effective way to prevent severe infection and decrease transmission.

Infants under 6 months of age are at high risk for life-threatening complications, but a vaccine for this age group is not yet in clinical trials; thus, maternal vaccination and breastfeeding may be an important strategy to protect infants. SARS-CoV-2 infection and vaccine immunity studies have focused predominantly on adults, but children have developing immune systems and may respond to the new mRNA vaccination platform differently from adults.

This proposal addresses the critical need to study the short- and long-term immune responses to COVID-19 mRNA vaccination in children, human milk, and breastfeeding infants. We have a successful ongoing longitudinal COVID-19 vaccination cohort that began in December 2020, in which we have collected biologic specimens from 368 individuals including adults, children, and lactating mother-infant pairs.

We will enroll a total of 560 individuals down to 6 months of age after the mRNA vaccine receives Emergency Use Authorization (EUA) for the younger age group. Participants are followed every 3 months for nasal, saliva, milk (if lactating), and blood samples. We will test all COVID-19 symptomatic or exposed participants for breakthrough infection throughout the study period.

Our central hypothesis is that the repertoire, magnitude, and longevity of COVID-19 vaccine-induced immune responses will be dependent on age and previous experience with SARS-CoV-2 infection. Importantly, our study will also move beyond the systemic immune responses to examine mucosal immunity in the respiratory tract and in human milk.

To test the hypothesis, we will characterize vaccine-induced serum, nasal, and saliva SARS-CoV-2-specific antibody response (Aim 1) and cellular (CD4+/CD8+) response (Aim 2) in children compared with adults and identify key immunologic correlates of protection against breakthrough infection. We will also determine humoral and cellular responses in human milk and secretory IgA in the breastfed infants' upper respiratory tract and evaluate vaccine-induced differential gene expression in milk that direct the immune response (Aim 3).

Our collaborative team with expertise in vaccinology, immunology, virology, epidemiology, and bioinformatics will ensure successful integrative analyses and interpretation of these immunologic and transcriptomic data. Completion of the study will provide a comprehensive characterization of longitudinal COVID-19 mRNA vaccination-induced immunity across age groups and in human milk to inform vaccination strategies to optimize the protection of children and infants.

San Diego University Of California

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]

La Jolla, California 920930626 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 299% from $800,605 to $3,195,734.