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Principal Investigator: Tian Wang
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2024
Award: $671,187
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY:
The Coronavirus disease 2019 virus (COVID-19) pandemic has made a devastating impact on global public
health and economy over the past three years. Despite the success in rapid progress of COVID-19 vaccine
development, increasing rates of variants of concern (VOCs) with enhanced viral transmission and disease
severity, and/or ability to escape vaccine-induced immunity have challenged the global vaccine efficiency
efforts. Continuous work toward optimizing existing vaccine platforms and development of more effective novel
vaccines is needed. Intranasal immunization can lead to the induction of antigen-specific immunity in both the
mucosal and systemic immune compartments, and thus is effective in control of SARS-CoV-2 infection and
disease. However, most SARS-CoV-2 vaccines granted for emergency use authorization or in clinical trials are
limited to parenteral delivery as soluble antigens do not breach the nasal epithelial barrier but are transported
by microfold cells. We recently reported that a modified porous silicon microparticle (mPSM) adjuvant to
SARS-CoV-2 receptor-binding domain (RBD) vaccine triggered potent and durable systemic humoral and type
1 helper T cell- mediated immune responses following parenteral vaccination. mPSM also facilitated mucosal
uptake of SARS-CoV-2 RBD antigens. Two doses of parenteral and intranasal combined vaccinations with
mPSM-RBD elicited more potent lung resident T and B cells and mucosal IgA responses than parenteral
vaccinations alone, which led to markedly diminished viral loads and inflammation in the lung following SARS-
CoV-2 Delta variant challenge. Our results suggest that mPSM is an effective adjuvant for SARS-CoV-2
subunit vaccine in both systemic and mucosal vaccinations. We also found that combinatorial mRNA-
S+Nucleocapsid (N) vaccination provided stronger protection against Delta and Omicron variants infection than
the clinically approved S-expressing mRNA vaccine alone. Thus, to further optimize the immunogenicity of
mPSM-adjuvanted subunit vaccine, we will modify the formulation of antigens. Here, we hypothesize that
parenteral and intranasal vaccination with mPSM-based subunit vaccine triggers durable systemic and
mucosal immune responses which provide cross protection against SARS-CoV-2 VOCs infection and
transmission. We will initially optimize the immunogenicity and test the safety of m-PSM subunit vaccines in
mice (Aim 1). Next, we will study the protective efficacy of parenteral and intranasal vaccination with m-PSM
subunit vaccine against SARS-CoV-2 VOCs infection in young and aged mice and identify the immune
correlates of host protection (Aim 2). Lastly, we will confirm the immunogenicity of m-PSM subunit vaccine in
hamsters and evaluate its efficacy on prevention of SARS-CoV-2 VOCs transmission and enhanced control of
infection (Aim 3). The result of this project will be an effective SARS-CoV-2 vaccine candidate that induces
balanced systemic and mucosal immunity, provides long-lived cross-reactive host protection against SARS-
CoV-2 VOCs, and prepares us for future coronavirus outbreaks.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Adjuvant><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><B.1.1.529><B.1.617.2><Binding Determinants><COVID-19><COVID-19 infection><COVID-19 transmission><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID-19 virus transmission><COVID19 infection><COVID19 virus><CV-19><Cell Body><Cells><Clinical><Clinical Trials><CoV-2><CoV2><Coronaviridae><Coronavirus><Coronavirus Infectious Disease 2019><Cricetinae><Delta variant><Disease><Disease Outbreaks><Disorder><Dose><Epithelial Cells><Epithelium><Epitopes><Exhibits><FDA EUA><FDA Emergency Use Authorization><FOLH><FOLH1><FOLH1 gene><Folate Hydrolase 1><Food and Drug Administration EUA><Food and Drug Administration Emergency Use Authorization><Formulation><Future><GCP2><Glutamate Carboxypeptidase II><Goals><Golden Hamsters><Golden Syrian Hamsters><Grant><Hamsters><Hamsters Mammals><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Human><IgA><Immune><Immune response><Immunes><Immunity><Immunization><Immunoglobulin A><Immunological response><Inducer Cells><Inducer T-Lymphocytes><Infection><Infection Control><Inflammation><Lung><Lung Respiratory System><Measures><Mediating><Mesocricetus auratus><Messenger RNA><Mice><Mice Mammals><Modeling><Modern Man><Mucosa><Mucosal Immune Responses><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Murine><Mus><N-Acetylated Alpha-Linked Acidic Dipeptidase 1><NAALAD1><NAALADase I><Nasal><Nasal Epithelium><Nasal Passages Nose><Nose><Nucleocapsid><Omicron variant><Outbreaks><PSM><PSMA><Population><Porosity><Prevention><Prostate-Specific Membrane Antigen><Proteins><Public Health><RNA vaccine><RNA-based vaccine><Reporting><Respiratory Epithelium><Respiratory System, Nose, Nasal Passages><Role><Route><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 B.1.1.529><SARS-CoV-2 B.1.617.2><SARS-CoV-2 delta><SARS-CoV-2 infection><SARS-CoV-2 omicron><SARS-CoV-2 omicron variant><SARS-CoV-2 transmission><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><Sarbecovirus><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><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><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 infection><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Si element><Silicon><Structure of respiratory epithelium><Subunit Vaccines><Syrian Hamsters><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><Testing><Toxic effect><Toxicities><Transmission><Vaccination><Vaccination acquired immunity><Vaccination induced immunity><Vaccine Antigen><Vaccines><Variant><Variation><Viral Burden><Viral Diseases><Viral Load><Viral Load result><Virus Diseases><Work><Wuhan coronavirus><aged mice><aged mouse><airway 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response><immunogen><immunogenicity><immunoresponse><in vivo><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><mRNA><mRNA vaccine><mRNA-based vaccine><mucosal uptake><mucosal vaccination><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><new vaccines><next generation vaccines><next outbreak><novel vaccines><old mice><omicron variant of COVID-19><omicron variant of SARS-CoV-2><outbreak in the future><pandemic virus><parenteral administration><parenteral delivery><parenteral infusion><particle><prevent><preventing><protective efficacy><pulmonary><receptor binding><receptor bound><respiratory tract epithelium><response><safety testing><severe acute respiratory syndrome coronavirus 2 B.1.1.529><severe acute respiratory syndrome coronavirus 2 B.1.617.2><severe acute respiratory syndrome coronavirus 2 transmission><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><success><thymus derived lymphocyte><transmission process><transmitted COVID-19><transmitted SARS-CoV-2><transmitted coronavirus disease 2019><transmitted severe acute respiratory syndrome coronavirus 2><uptake><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 candidate><vaccine candidates against SARS-CoV-2><vaccine development><vaccine for novel coronavirus><vaccine platform><vaccine-induced immunity><vaccine-induced protection><vaccines preventing COVID><vaccines to prevent COVID><variants of concern><viral infection><viral transmission><virus infection><virus transmission><virus-induced disease><β CoV><β coronavirus><βCoV>