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Principal Investigator: Hilliard Kutscher
Organization: POP BIOTECHNOLOGIES, INC
Fiscal Year: 2024
Award: $950,225
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Influenza is the cause of considerable morbidity and mortality globally. Despite immunization being the most
effective and economical prophylactic approach, vaccines often provide less than optimal defense against an
influenza virus infection and illness. While hemagglutinin (HA) is the primary target of influenza vaccines, it is
also known that the other major surface protein, neuraminidases (NA) induces protective antibodies. This Direct
to Phase 2 SBIR proposal continues our development and characterization of a unique vaccine platform that has
been formulated by POP BIO. This platform consists of fabricating lipid bilayer nanoliposomes with a cobalt-
porphyrin moiety intercalated into the bilayer (CoPoP) along with a monophosphoryl lipid A, a TLR4-based
vaccine adjuvant, and a saponin QS-21. CoPoP enables spontaneous nanoliposome adjuvant particle formation
(SNAP). When SNAP liposomes are combined with his-tagged recombinant trimeric HAs and tetrameric NAs, a
mosaic nanoparticle vaccine candidate, SNAP-Flu is formed. The his-tag stably inserts into the bilayer by
association with the cobalt producing nanoliposomes decorated with the immunogenic influenza antigens. In
preliminary data, we have established that HA and NA protect mice from lethal H1N1, H3N2 and B strain inflenza
virus challenge, while even better protection is observed with the multivalent SNAP-Flu nanoparticle vaccine. It
has also been shown that this platform allows for the use of much less antigen in the vaccine (antigen sparing)
in addition to the capacity for multiplexing with numerous antigens from different influenza strains. This study will
involve POP BIO producing and characterizing the physical and chemical properties of SNAP-Flu. POP BIO will
interact with the University at Buffalo, BIOQUAL, and Texas Biomedical Research Institute to assess the level
of protection of SNAP-Flu against challenge with mouse-adapted strains of influenza in mice, human influenza
strains in ferrets, and human influenza strains in non-human primates. The amount of antigen-sparing will be
determined as will head-to-head comparison with other commercially available influenza vaccine formulations.
This Direct to Phase 2 SBIR proposal will expand development of this platform to novel influenza antigen designs
in preparation for clinical translation.
Terms: <2019-nCoV vaccine><Acute><Acylneuraminyl hydrolase><Adjuvant><Agonist><Animals><Antibodies><Antigens><Baculoviridae><Baculovirus Expression System><Baculoviruses><Biomedical Research><Biotech><Biotechnology><COVID-19 vaccine><Cell Body><Cells><Cessation of life><Chemistry><Clinical Trials><Cobalt><Coupling><Data><Data Set><Death><Development><Domestic Rabbit><Dose><Engineering><Ferrets><Goals><Grippe><H1N1><H1N1 Virus><H3N2><H3N2 Virus><Hemagglutinin><Histidine><Homolog of Drosophila TOLL><Human><Immune response><Immunization><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Infection><Influenza><Influenza A Virus, H1N1 Subtype><Influenza A Virus, H3N2 Subtype><Influenza Vaccines><Influenza Virus><Influenza prevention><Insecta><Insects><Insects Invertebrates><Lipid A><Lipid Bilayers><Liposomal><Liposomes><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Mice><Mice Mammals><Modeling><Modern Man><Modernization><Morbidity><Morbidity - disease rate><Murine><Mus><N-Acylneuraminate Glycohydrolases><Neuraminidase><Oligosaccharide Sialidase><Oryctolagus cuniculus><Phase><Phosphatides><Phospholipids><Play><Population><Porphyrins><Position><Positioning Attribute><Preparation><Process><Production><Proteins><Publishing><QS 21><QS-21 Adjuvant><QS21><Rabbits><Rabbits Mammals><Recombinant Vaccines><Recombinants><Recommendation><Reporting><Research Institute><Role><SARS-CoV-2 vaccine><SARS-coronavirus-2 vaccine><SBIR><Saponins><Seasons><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vaccine><Severities><Sialidase><Small Business Innovation Research><Small Business Innovation Research Grant><Stimulon QS-21 Adjuvant><Surface><Surface Proteins><System><TLR4><TLR4 gene><Technology><Testing><Texas><Toll Homologue><Toxic effect><Toxicities><Translations><Universities><Vaccination><Vaccine Adjuvant><Vaccines><Viral><Viral Antigens><Virus><chemical property><clinical candidate><clinical translation><clinically translatable><coronavirus disease 2019 vaccine><coronavirus disease-19 vaccine><design><designing><developmental><egg><exo alpha sialidase><flu><flu infection><flu prevention><flu serotype><flu strain><flu subtype><flu vaccine><flu viral strain><flu virus infection><flu virus strain><flu virus vaccine><head-to-head analysis><head-to-head comparison><host response><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><improved><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><influenza infection><influenza serotype><influenza strain><influenza subtype><influenza viral strain><influenza virus infection><influenza virus strain><influenza virus vaccine><influenzavirus><intercalation><lipid bilayer membrane><manufacture><mortality><mosaic><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nano particle><nano-sized particle><nanoliposomal><nanoliposome><nanoparticle><nanosized particle><next generation><non-human primate><nonhuman primate><novel><particle><phase 2 trial><phase II trial><physical property><pre-clinical><preclinical><preparations><prevent influenza><prophylactic><protective efficacy><response><scale up><seasonal flu><seasonal influenza><social role><stability testing><technology platform><technology system><toll-like receptor 4><translation><translational opportunities><translational potential><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 against flu><vaccine against influenza><vaccine candidate><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccine formulation><vaccine platform><vaccines preventing COVID><vaccines to prevent COVID><virus antigen>