The current global pandemic has highlighted the need to develop new methods for creating vaccines. Many approaches today face limitations with breadth and duration of protection; flexibility and adaptability for emerging strains; manufacturing speed and safety; and storage and distribution. SolaVAX inactivation technology offers an elegant solution for quickly generating highly effective vaccines by using a combination of a photosensitizer (riboflavin/vitamin B2) and UV light to disrupt pathogen genetic material while preserving target antigens. Likely advantages of SolaVAX-derived vaccines include: more complete antigen presentation using whole pathogens; multiple virus strains/ multiple antigen variants, i.e. multivalent; rapid manufacturing pivot to address emergent strains; no toxic inactivating chemicals that potentially compromise antigen conformation and add to manufacturing complexity; low cost, geographically distributed manufacturing; applicable to viral, bacterial and parasitic pathogens. In recent work supported by BARDA and NIH, Drs. Raymond Goodrich and Izabela Ragan demonstrated that a SolaVAX-SARS-CoV-2 vaccine dramatically decreased viral load, reduced lymphocytic infiltration and neutrophil accumulation, and maintained lung alveolar air space after virus exposure. From these studies, the SolaVAX-SARS-CoV-2 investigational vaccine is estimated to be up to 20,000x more effective on a weight/weight basis of dose compared to other inactivation methods. This SBIR project will focus on the evaluation of the SolaVAX approach for creating improved influenza vaccines composed of whole inactivated virions. Although global attention has been focused on COVID-19 since 2020, the pandemic threat of influenza still exists. Moreover, the risk of a pandemic influenza may be exacerbated by SARS-CoV-2, given the burden on global healthcare systems and increased number of individuals with pre- existing conditions, such as compromised respiratory systems. Current flu vaccines provide sub-optimal protection (40-60%) and improved approaches for multi-strain and/or universal protection are needed. In promising preliminary in vitro studies, a SolaVAX-generated influenza vaccine provided 70-80% retention of hemagglutinin (HA) activity, as compared to 40-45% after inactivation by formalin. Phase I of this project will build on these studies to establish the vaccine development process that yields full inactivation with maximal antigen integrity (AIM 1). Then, we will evaluate inactivated vaccine for immunogenicity in mice (AIM 2) and efficacy against live viral challenge in ferret (AIM 3).
Public Health Relevance Statement: Project narrative: The current global pandemic has highlighted the need to develop improved methods for creating vaccines. SolaVAX technology uses a combination of a photosensitizer (riboflavin/vitamin B2) and UV light to disrupt pathogen genetic material while preserving target antigens. This proposal will evaluate the SolaVAX method for production of a safe, effective, and broadly protective influenza vaccine.
Project Terms: immunoglobulin biosynthesis; Antibody Formation; immunogen; Antigens; virus antigen; Viral Antigens; Attention; Biological Assay; Assay; Bioassay; Biologic Assays; Blood; Blood Reticuloendothelial System; Colorado; Disease; Disorder; Enzyme-Linked Immunosorbent Assay; ELISA; enzyme linked immunoassay; Enzymes; Enzyme Gene; Face; faces; facial; Ferrets; Geography; Growth; Generalized Growth; Tissue Growth; ontogeny; Cyclic GMP; Guanosine Cyclic Monophosphate; cGMP; Healthcare Systems; Health Care Systems; Hemagglutinin; Immunization; In Vitro; Infection; Influenza; Grippe; influenza virus vaccine; Influenza Vaccines; flu vaccine; flu virus vaccine; vaccine against flu; vaccine against influenza; Kinetics; Lectin; Lung; Lung Respiratory System; pulmonary; Methods; Molecular Conformation; Molecular Configuration; Molecular Stereochemistry; conformation; conformational; conformational state; conformationally; conformations; Mus; Mice; Mice Mammals; Murine; United States National Institutes of Health; NIH; National Institutes of Health; Neuraminidase; Acylneuraminyl hydrolase; N-Acylneuraminate Glycohydrolases; Oligosaccharide Sialidase; Sialidase; exo alpha sialidase; Neutralization Tests; antibody neutralization test; neutrophil; Blood Neutrophil; Blood Polymorphonuclear Neutrophil; Marrow Neutrophil; Neutrophilic Granulocyte; Neutrophilic Leukocyte; Polymorphonuclear Cell; Polymorphonuclear Leukocytes; Polymorphonuclear Neutrophils; Nose; Nasal; Nasal Passages Nose; Respiratory System, Nose, Nasal Passages; Nucleoproteins; Plaque Assay; Poison; Toxic Chemical; Toxic Substance; toxic compound; Production; Proteins; Resources; Research Resources; Respiratory System; Respiratory tract structure; Pulmonary Body System; Pulmonary Organ System; Respiratory Tracts; Riboflavin; Vitamin B 2; Vitamin B2; Vitamin G; Risk; Safety; Technology; Testing; Tissues; Body Tissues; Trachea; Trachea Proper; windpipe; Ultraviolet Rays; Actinic Rays; UV light; UV radiation; UV rays; ultra violet light; ultra violet radiation; ultra violet rays; ultraviolet light; ultraviolet radiation; Universities; Vaccines; Inactivated Vaccines; Inactivated Virus Vaccine; Killed Vaccines; Viral Proteins; Viral Gene Products; Viral Gene Proteins; virus protein; Virion; Virus Particle; Virus; Weight; weights; Work; Photosensitizers; photosensitizer; Photosensitizing Agents; Blood Sample; Blood specimen; improved; Phase; Variation; Variant; Antigen Presentation; Link; Chemicals; Evaluation; Individual; Trademark; Lymphocytic Infiltrate; Viral Load result; Viral Burden; Viral Load; Genetic Materials; Intramuscular; System; Antibody titer measurement; antibody titering; Viral; respiratory; vaccine development; develop a vaccine; develop vaccines; development of a vaccine; Animal Model; Animal Models and Related Studies; model of animal; Histopathology; Speed; General Population; General Public; Modeling; Sampling; Vascular blood supply; blood supply; vascular supply; Formalin; Influenza A virus; Influenza A; Influenza Viruses Type A; Influenzavirus A; Orthomyxovirus Type A; Type A Influenza; Influenza B Virus; Influenza B; Influenza Viruses Type B; Orthomyxoviruses Type B; evaluate vaccines; vaccine screening; vaccine testing; vaccine evaluation; Conchae Nasales; Turbinates; Nasal turbinate bone structure; influenzavirus; Influenza Virus; Alveolar; Address; Dose; global health; Protein Analysis; in vivo; Antigen Targeting; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Vaccinated; Vaccine Production; produce vaccines; Process; Development; developmental; Influenza A Virus, H3N2 Subtype; H3N2; H3N2 Virus; Influenza A Virus, H1N1 Subtype; H1N1; H1N1 Virus; pandemic disease; pandemic; flu virus pandemic; influenza virus pandemic; pandemic flu; pandemic strain of influenza; pandemic influenza; cost; determine efficacy; efficacy analysis; efficacy assessment; efficacy determination; efficacy examination; evaluate efficacy; examine efficacy; efficacy evaluation; pathogen; new vaccines; next generation vaccines; novel vaccines; vaccine candidate; manufacturing process development; flexible; flexibility; Formulation; efficacy study; preservation; COVID19; CV-19; CV19; corona virus disease 2019; coronavirus disease 2019; coronavirus disease-19; coronavirus infectious disease-19; COVID-19; 2019 novel corona virus; 2019 novel coronavirus; COVID-19 virus; COVID19 virus; CoV-2; CoV2; SARS corona virus 2; SARS-CO-V2; SARS-COVID-2; SARS-CoV-2; SARS-CoV2; SARS-associated corona virus 2; SARS-associated coronavirus 2; SARS-coronavirus-2; 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-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 related corona virus 2; Wuhan coronavirus; coronavirus disease 2019 virus; coronavirus disease-19 virus; hCoV19; nCoV2; 2019-nCoV; 2019-nCoV vaccine; COVID19 vaccine; SARS-CoV-2 vaccine; SARS-CoV2 vaccine; SARS-coronavirus-2 vaccine; Severe Acute Respiratory Syndrome CoV 2 vaccine; Severe acute respiratory syndrome coronavirus 2 vaccine; corona virus disease 2019 vaccine; coronavirus disease 2019 vaccine; coronavirus disease-19 vaccine; nCoV vaccine; nCoV-19 vaccine; nCoV19 vaccine; 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 for novel coronavirus; COVID-19 vaccine; antibody assay; antibody based test; antibody test; vaccine immunogenicity; vaccine immune response; pandemic response; pandemic containment; pandemic control; pandemic mitigation; prevent pandemics; pandemic prevention; new pandemic; emergent pandemic; emerging pandemic; novel pandemic; pandemic potential; pandemic concern; pandemic risk; pandemic threat; manufacture; technology platform; technology system; Air; Animals; Ab response; Antibody Production; antibody biosynthesis
