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Principal Investigator: Marian L Kohut
Organization: IOWA STATE UNIVERSITY
Fiscal Year: 2024
Award: $191,250
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY / ABSTRACT
Vaccination is an effective public health measure, yet host factors including advanced age, sex, obesity,
physical or mental health status may influence vaccine efficacy. Adjuvants improve immunogenicity to
vaccination but often result in greater side effects. As an alternative to the inclusion of adjuvants in the vaccine
formulation, evidence suggests physical exercise performed at the time of immunization may serve as an
effective non-pharmacological approach with the potential for greater impact in individuals with suboptimal
immune response and reduced reactogenicity. The effect of host factors on immune response to SARS-CoV-2
and long-term protection remains to be established, and positive findings for an adjuvant-like effect of physical
exercise would have an immediate translational impact. However, major barriers to the implementation of
exercise are inconsistent findings and a gap in the knowledge of the mechanisms that underlie such effects. Our
recent publication shows that we have identified an exercise protocol that consistently increases antibody
response to vaccines that is reproducible across several different vaccines. This finding holds the potential to
transform vaccine efficacy and address questions on the breadth and durability of immune response and
underlying mechanisms. The goals of this application are to determine the extent to which physical exercise
exhibits an adjuvant-like effect across long-term antibody and T cell-mediated immune responses to COVID-19
mRNA-based vaccines and establish the degree of immune enhancement in individuals who may have
suboptimal vaccine response due to high psychological stress. An additional goal is to identify potential operative
mechanisms, and compelling preliminary data show promise for metabolism-related mechanisms, a new
direction in this field of study. Aim 1 will identify the extent to which a single exercise session applied at the time
of initial immunization shapes the magnitude, breadth, and durability of immune response to SARS-CoV-2 mRNA
vaccine. Outcome measures are serum anti-spike receptor-binding domain (RBD) IgG titer, neutralizing
antibody, antigen-specific CD4+ and CD8+ T cell response measured up to one-year post-immunization. Aim 2
will determine the influence of psychological stress on antibody and antigen-specific CD4+ and CD8+ T cell
immune response to SARS-CoV-2 immunization and the extent to which exercise may override any potential
effect of stress. Aim 3 will apply transcriptomic (RNA-Seq) and metabolomic (Raman) measures to identify
pathways by which exercise influences immune response to vaccination. The long-term goals of this research
direction are to refine and develop behavioral interventions that optimize immunity and more broadly apply the
findings learned with respect to critical pathways of immunogenicity to optimize vaccine development for
currently underserved populations.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><7S Gamma Globulin><> 65 years><Acute><Address><Adjuvant><Aged 65 and Over><Antibodies><Antibody Response><Antigens><BNT 162b2><BNT162b2><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral Conditioning Therapy><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Blood Serum><Body Weight><Buffers><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID-19><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID19 virus><CV-19><Cellular Metabolic Process><Chronic><CoV-2><CoV2><Complex><Conditioning Therapy><Coronavirus Infectious Disease 2019><Critical Paths><Critical Pathways><Data><Dendritic Cells><Dose><Elderly><Exercise><Exhibits><Formulation><Gene Expression><Glucocorticoids><Goals><Health Status><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Host Factor><Host Factor Protein><IR/UV/Raman Spectroscopy><IgG><Immune><Immune Cell Activation><Immune memory><Immune response><Immunes><Immunity><Immunization><Immunoglobulin G><Immunologic Memory><Immunological Memory><Immunological response><Impairment><Individual><Inducer Cells><Inducer T-Lymphocytes><Integration Host Factors><Intermediary Metabolism><Knowledge><Learning><Level of Health><Literature><Maps><Measures><Mental Health><Mental Hygiene><Messenger RNA><Metabolic><Metabolic Processes><Metabolism><Modeling><Moderna COVID-19 vaccine><Moderna coronavirus disease 2019 vaccine><Non-pharmacologic Therapy><Nonpharmacologic Intervention><Nonpharmacologic Therapy><Nonpharmacologic approach><Nonpharmacologic treatment><Obesity><Outcome Measure><Pathway interactions><Patient Self-Report><Pfizer covid19 vaccine><Pfizer-BioNTech COVID-19 vaccine><Pfizer-BioNTech coronavirus disease 2019 vaccine><Pfizer/BioNTech vaccine><Physical Exercise><Population><Position><Positioning Attribute><Protocol><Protocols documentation><Psychologic Stress><Psychological Health><Psychological Stress><Psychosocial Stress><Public Health><Publications><RNA Seq><RNA sequencing><RNA vaccine><RNA-based vaccine><RNAseq><Raman Spectroscopy><Raman Spectrum Analysis><Raman imaging><Raman spectrometry><Reporting><Reproducibility><Research><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scientific Publication><Self-Report><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Shapes><Spikevax><Standardization><Stress><Survey Instrument><Surveys><T cell response><T memory cell><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Time><Underserved Population><Vaccination><Vaccines><Veiled Cells><Wuhan coronavirus><above age 65><adiposity><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged 65 and greater><aged 65+><aged ≥65><anamnestic reaction><barriers to implementation><behavior intervention><behavioral intervention><bench-to-bedside translation><cell mediated immune response><cell metabolism><cellular metabaolism><coronavirus disease 2019><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><corpulence><cytokine><develop a vaccine><develop vaccines><development of a vaccine><field based data><field learning><field study><field test><geriatric><hCoV19><health level><host response><human old age (65+)><immune activation><immune response to vaccination><immune response to vaccines><immune system response><immunogen><immunogenicity><immunoresponse><implementation barriers><implementation challenges><improved><insight><mRNA><mRNA vaccine><mRNA-1273><mRNA-based vaccine><mRNA1273><measurable outcome><memory T lymphocyte><metabolic profile><metabolism measurement><metabolomics><metabonomics><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neutralizing antibody><non-drug therapy><non-drug treatment><nondrug therapy><nondrug treatment><novel><old age><outcome measurement><over 65 years><pathogen><pathway><perceived stress><perception of stress><physical conditioning><physical health><receptor binding><receptor bound><response><secondary immune response><self-reported stress><senior citizen><sex><side effect><stress perception><thymus derived lymphocyte><transcriptome sequencing><transcriptomic sequencing><transcriptomics><translational applications><translational impact><under served group><under served individual><under served people><under served population><underserved group><underserved individual><underserved people><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine candidates against SARS-CoV-2><vaccine development><vaccine efficacy><vaccine for novel coronavirus><vaccine formulation><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine response><vaccine responsiveness><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><≥65 years>