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Principal Investigator: Pia S Pannaraj
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2023
Award: $789,998
Funding agency: National Institute of Allergy and Infectious Diseases
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 infects. 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.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><21+ years old><7S Gamma Globulin><Address><Adolescent><Adolescent Youth><Adult><Adult Human><Age><Age Months><Antibodies><Antibody Response><Antigenic Determinants><Assay><BNT 162b2><BNT162b2><Bar Codes><Binding Determinants><Bio-Informatics><Bioassay><Bioinformatics><Biologic Assays><Biological><Biological Assay><Blood Sample><Blood Serum><Blood specimen><Breast Feeding><Breast Milk><Breast fed><Breast fed infant><Breastfed><Breastfed infant><Breastfeeding><Breastmilk><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19><COVID-19 antibody><COVID-19 exposure><COVID-19 immunity><COVID-19 infection><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 immunity><COVID19 infection><COVID19 vaccination><COVID19 vaccine><COVID19 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RNA><Maternal mRNA><Measures><Methods><Milk><Mother's Milk><Mothers><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Nasal><Nasal Mucosa><Nasal Passages Nose><Non-Polyadenylated RNA><Nose><PBMC><Participant><Pathway interactions><Peripheral Blood Mononuclear Cell><Pfizer-BioNTech COVID-19 vaccine><Pfizer-BioNTech coronavirus disease 2019 vaccine><Policy Maker><Population><Proteins><Pulmonary Body System><Pulmonary Organ System><RNA><RNA Expression><RNA Gene Products><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><RT-PCR><RTPCR><Recording of previous events><Research Specimen><Respiratory System><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Reverse Transcriptase Polymerase Chain Reaction><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 exposure><SARS-CoV-2 immunity><SARS-CoV-2 infection><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 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respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Site><Source><Specimen><Staining method><Stains><Structure of mucous membrane of nose><System><T cell receptor repertoire sequencing><T cell receptor sequencing><T cell response><T-Cell Activation><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><TCR repertoire sequencing><TCR sequencing><TCR-seq><TCRseq><Testing><Time><Tissue-Specific Differential Gene Expression><Tissue-Specific Gene Expression><Transcription><Transmission><United States><Up-Regulation><Upper respiratory tract><Upregulation><Vaccination><Vaccines><Viral><Whole Blood><Wuhan coronavirus><activate T cells><adulthood><age group><ages><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody-based immunity><barcode><biologic><breakthrough infection><breast feeding infant><breastfeeding infant><cohort><community spread><community transmission><community-level spread><community-level transmission><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 exposure><coronavirus disease 2019 immunity><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><emergency use authorization><enroll><enzyme linked immunoassay><epidemiologic><epidemiological><evaluate vaccines><experience><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><hCoV19><high risk><histories><host response><immune system response><immunity against COVID-19><immunity against COVID19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to COVID19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunization strategy><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><juvenile><juvenile human><kids><lactating><lactational><life span><lifespan><mRNA immunization><mRNA vaccination><mRNA vaccine><mRNA-based 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2019><vaccination strategy><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine evaluation><vaccine for novel coronavirus><vaccine screening><vaccine testing><vaccinology><virology><youngster>