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Principal Investigator: Maria Cristina Gingerich
Organization: CYANVAC, LLC
Fiscal Year: 2023
Award: $249,999
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
In this Phase I SBIR application, we propose to develop an intranasal, parainfluenza virus 5 (PIV5)-based human
metapneumovirus (HMPV) vaccine. HMPV is one of the leading causes of acute respiratory infections (ARIs) in
children, immunocompromised individuals, and the elderly. Illness ranges from asymptomatic infection to severe
bronchiolitis and pneumonia, with 90-100% of children infected between the ages of 5-10 years old. No licensed
HMPV vaccine is available and there is an unmet medical need to develop a safe and effective HMPV vaccine.
PIV5 is a safe delivery vector for intranasal immunization. The PIV5-vectored COVID-19 vaccine (CVXGA1) and
respiratory syncytial virus (RSV, a leading cause of lower respiratory tract infection in infants and elderly) vaccine
are currently in Phase 1 clinical testing. Preclinical data for PIV5-based RSV candidate vaccines have shown
excellent immunogenicity, protection, and safety profiles in various animal models, including the cotton rat model,
demonstrating lack of vaccine-induced enhanced disease observed following formalin-inactivated RSV
vaccination. In this grant proposal, we will produce two PIV5-based HMPV candidate vaccine constructs, one in
the W3A strain with the SH gene deleted (W3A!SH-HMPV-F) and another in the canine parainfluenza virus
(CPI) vaccine strain (CPI-HMPV-F) to compare their replication in vitro, antigen expression in vitro,
immunogenicity, and protection against HMPV challenge infection in a mouse model. The novelty of the vaccine
proposed in this Phase I SBIR application relates to: 1) the use of a chimeric HMPV F protein containing the
PIV5 F cytoplasmic tail to potentially increase HMPV F antigen exposure on the virion surface 2) a needle-free
intranasal delivery method in a safe, highly immunogenic viral vector and 3) the ability to induce mucosal
immunity, which is necessary for protecting against respiratory pathogens. Once the PIV5-vectored HMPV
vaccine is demonstrated to be immunogenic in the mouse model, the Phase II SBIR proposal will focus on
preclinical studies needed for entering Phase 1 clinical trials with the final goal of generating a bivalent PIV5-
vectored RSV and HMPV vaccine which would provide protection against the two leading causes of lower
respiratory tract infections in infants and elderly.
Terms: <0-11 years old><10 year old><10 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><Acute respiratory infection><Adenoviridae><Adenoviruses><Age><Amino Acid Sequence><Animal Model><Animal Models and Related Studies><Antibodies><Antigens><Applications Grants><Assay><Attenuated><BALB C Mouse><BALB/c><Bioassay><Biologic Assays><Biological Assay><Blood Serum><Blood group antigen f><Bronchiolitis><COVID-19 S protein><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccine><COVID-19 virus><COVID19 S protein><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccine><COVID19 virus><Canine Species><Canis familiaris><Cell Body><Cells><Child><Child Youth><Children (0-21)><Classification><Clinical Evaluation><Clinical Testing><Clinical Treatment Moab><CoV-2><CoV2><Cotton Rats><Cytoplasmic Domain><Cytoplasmic Tail><Data><Disease><Disorder><Distemper><Dogs><Dogs Mammals><Dose><Early-Stage Clinical Trials><Elderly><Equilibrium><F antigen><Family><Formalin><G-Proteins><GTP-Binding Proteins><GTP-Regulatory Proteins><Gene Deletion><Gene Proteins><Generalized Growth><Genes><Genetic><Genome><Glycoproteins><Goals><Grant Proposals><Growth><Guanine Nucleotide Coupling Protein><Guanine Nucleotide Regulatory Proteins><Hospital Admission><Hospitalization><Human><Human Metapneumovirus><Immune response><Immunization><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunofluorescence><Immunofluorescence Immunologic><Immunological response><Immunosuppressed Host><In Vitro><Inbred BALB C Mice><Individual><Infant><Infection><Influenza Virus><Kinetics><Licensing><Lower Respiratory Tract Infection><Lower respiratory infection><Lower respiratory tract structure><Medical><Methods><Modeling><Modern Man><Monoclonal Antibodies><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Needles><Non-Polyadenylated RNA><Parainfluenza><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Pneumonia><Pneumoviridae><Pneumovirinae><Pneumovirus><Primary Protein Structure><Protein Gene Products><Proteins><Public Health><RNA><RNA Gene Products><RSV Vaccines><Recombinant Viral Vaccine><Regimen><Respiratory Syncytial Virus Vaccines><Respiratory syncytial virus><Rhinovirus><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-CoV2 vaccine><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><SBIR><Safety><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 S protein><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><Small Business Innovation Research><Small Business Innovation Research Grant><Spinal Column><Spine><Surface><Symptoms><Systematics><Testing><Tissue Growth><Upper Respiratory Infections><Upper Respiratory Tract Infection><Upper respiratory tract><Vaccination><Vaccines><Vero Cells><Vertebral column><Vial><Vial device><Viral Vector><Virion><Virus><Virus Particle><Wuhan coronavirus><advanced age><age 10 years><ages><attenuate><attenuates><backbone><balance><balance function><canine><child patients><clinical test><combat><corona virus disease 2019 vaccine><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cross immunity><cross protection><delivery vector><delivery vehicle><develop a vaccine><develop vaccines><development of a vaccine><domestic dog><elderly patient><elders><gene deletion mutation><geriatric><hCoV19><host response><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><immunosuppressed patient><in vivo evaluation><in vivo testing><influenzavirus><kids><late life><later life><lead candidate><lower respiratory tract><mAbs><model of animal><monoclonal Abs><mouse model><murine model><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><novel><older adult><older patient><older person><ontogeny><parainfluenza virus><pathogenic virus><pediatric patients><phase I protocol><plasmid vaccine><pre-clinical><pre-clinical study><preclinical><preclinical study><programs><protective efficacy><protein expression><protein sequence><recombinant virus vaccine><research clinical testing><respiratory pathogen><senior citizen><success><ten year old><ten years of age><upper airway tract><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 candidate><vaccine development><vaccine efficacy><vaccine for novel coronavirus><vaccine immune response><vaccine immunogenicity><vector><vector vaccine><viral pathogen><virus pathogen><youngster>