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Principal Investigator: RAJENDAR K DEORA
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2024
Award: $769,833
Funding agency: National Institute of Allergy and Infectious Diseases
With the emergence of SARS-CoV-2 variants with mutations in the Spike protein, there remains an urgent need
for vaccines that are both effective against variants and that generate long-lived mucosal immunity. Generation
of durable cell-mediated and humoral immunity is critical for optimal naturally occurring and vaccine-induced
protection against respiratory pathogens, including SARS-CoV-2, and includes IFN-γ and IL-17 producing tissue-
resident memory T (TRM) cells, T follicular helper (TFH) cells, germinal center (GC) and memory B cells, that
contribute to the production of pathogen-specific neutralizing antibodies.
Most currently approved vaccines are adjuvanted with alum, which is a strong adjuvant that elicits TH2 skewed
cellular and humoral responses, associated with short-lived immunity to intracellular respiratory pathogens.
Experimental adjuvants that generate TH1 and TH17 driven systemic and mucosal responses, provide effective
and long-lived protection against infection.
Bordetella Colonization Factor A (BcfA) is an adjuvant that elicits strong TH1 and TH17 responses and has the
unique ability to attenuate the detrimental TH2 responses primed by alum. Polyfunctional IL-21 and IFN-γ (TFH1
cells) or IL-21 and IL-17 (TFH17 cells) cells are important for generation of effective antibodies against viral
respiratory pathogens. The TH1/TH17 skewing properties of BcfA may promote the differentiation and function of
these specialized TFH cell populations.
Mucosal vaccination is a more effective means of generating tissue-resident memory that is not generated by
parenterally administered alum-adjuvanted vaccines. A prime-pull regimen (systemic priming and intranasal
booster) generates mucosal responses to vaccines containing TH1/TH17 skewing adjuvants and provides
superior protection. We will test the overarching hypothesis that a BcfA/alum-adjuvanted subunit SARS
CoV-2 vaccine containing S, M and N proteins, delivered via a heterologous prime-pull immunization regimen
will reduce SARS-CoV-2 infection of the mouse respiratory tract and elicit long-lived systemic and
mucosal TH1/TH17 driven immune responses.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><Adjuvant><Adoptive Transfer><Adult><Adult Human><Alum Adjuvant><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antigens><Attenuated><Avidity><B pertussis><B. pertussis><Blocking Antibodies><Body Tissues><Bordetella><Bordetella pertussis><CD8><CD8B><CD8B1><CD8B1 gene><COVID-19 S protein><COVID-19 infection><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CTLA-8><CTLA-8 Gene><CTLA8><CTLA8 Gene><Cell Body><Cell secretion><Cells><Cellular Secretion><Class Switching><Class Switchings><Co(beta)-cyano-7''-(2-methyl)adeninylcobamide><CoV-2><CoV2><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Antigen 8 Gene><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8 Gene><Data><Development><Formulation><Generations><Genetic Alteration><Genetic Change><Genetic defect><Germinal Center><Golden Hamsters><Golden Syrian Hamsters><H Pertussis><H. Pertussis><Haemophilus pertussis><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Human><Humoral Immunities><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-17><IL-17 Gene><IL-17A><IL-17A Gene><IL17><IL17 Protein><IL17 gene><IL17A><IL17A Gene><IL21><Immune><Immune Interferon><Immune response><Immunes><Immunity><Immunization><Immunoglobulin Class Switching><Immunoglobulin Class Switchings><Immunological response><Inducer Cells><Inducer T-Lymphocytes><Infection><Inflammatory><Interferon Gamma><Interferon Type II><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8) Gene><Interleukin 17 Precursor><Interleukin 17 Precursor Gene><Interleukin-17><Intramuscular><Isotype Switching><Isotype Switchings><K-18><K-18 conjugate><K18><K18 combination><KO mice><Knock-out Mice><Knockout Mice><LYT3><Laboratories><Location><Lung><Lung Respiratory System><M tb><M tuberculosis><M. tb><M. tuberculosis><Mediating><Memory><Memory B Cell><Memory B-Lymphocyte><Mesocricetus auratus><Messenger RNA><Mice><Mice Mammals><Modeling><Modern Man><Mouse Strains><Mucosa><Mucosal Immune Responses><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mutation><Mycobacterium tuberculosis><Nasal><Nasal Passages Nose><Nature><Nose><Nucleocapsid><Null Mouse><Pasteurella pestis><Pathology><Phenotype><Play><Population><Production><Productivity><Property><Proteins><Publishing><Pulmonary Body System><Pulmonary Organ System><Regimen><Respiratory System><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Role><Route><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 infection><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 infection><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><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 S protein><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Shapes><Structural Protein><Structure of germinal center of lymph node><Subunit Vaccines><Syrian Hamsters><T cell response><T memory cell><T-Cells><T-Lymphocyte><Testing><Tissues><Transgenic Organisms><Vaccination acquired immunity><Vaccination induced immunity><Vaccine Design><Vaccines><Variant><Variation><Viral><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Work><Wuhan coronavirus><Y pestis><Y. pestis><Yersinia pestis><adulthood><alum><aluminum sulfate><antibody-based immunity><attenuate><attenuates><bacteria pathogen><bacterial pathogen><coronavirus disease 2019 S protein><coronavirus disease 2019 infection><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cytokine><deliver vaccines><developmental><experiment><experimental research><experimental study><experiments><factor A><genome mutation><hCoV19><host response><immune system response><immunization strategy><immunogen><immunoresponse><improved><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><interleukin-21><lFN-Gamma><mRNA><memory T lymphocyte><model of animal><mtb><mucosal vaccination><mucosal vaccine><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neutralizing antibody><novel><parenteral administration><parenteral delivery><parenteral infusion><pathogen><pathogenic bacteria><pathogenic virus><protective efficacy><pulmonary><resident memory T cell><respiratory><respiratory pathogen><response><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><social role><spike proteins on SARS-CoV-2><thymus derived lymphocyte><tissue resident memory T cell><transgenic><translational impact><vaccination strategy><vaccine acquired immunity><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 immunity><vaccine candidates against SARS-CoV-2><vaccine delivery><vaccine efficacy><vaccine for novel coronavirus><vaccine-induced immunity><vaccine-induced protection><vaccines preventing COVID><vaccines to prevent COVID><variants of concern><viral pathogen><virus pathogen><virus protein>