SBIR-STTR Award

The coronavirus disease 2019 (COVID-19) global pandemic caused by Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2) is unprecedented in our lifetime and has caused major social, economic andhuman suffering. Globally, there have been 76,858,506 confirmed cases, leading to 1,711,498 deaths asreported by the WHO through December 2020. The rollout of FDA-authorized Pfizer (-80 ˚C storage) andModerna (-20 ˚C storage) vaccines has highlighted the challenges posed by low requisite storage temperatures.Elimination of cold chain requirements for emerging vaccine solutions could facilitate distribution and provideconsiderable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposesto investigate a lyophilization strategy for its novel vaccine adjuvant platform that induces spontaneous antigenparticles, using the receptor-binding domain (RBD) of the SARS CoV-2 spike (S) protein. We were amongst thefirst to show that a liquid form of RBD particles potently increases SARS-CoV-2 neutralizing antibodies by ordersof magnitude compared to the soluble antigen. Our vaccine platform induces the particle formation of well-characterized his-tagged antigens by simple admixing with liposomes that contain small amounts of cobaltporphyrin-phospholipid (CoPoP) and the clinical adjuvants monophosphoryl lipid A and QS-21. CoPoPliposomes give rise to rapid antigen particleization that is stable in biological media. In this collaborative Phase ISBIR proposal, we will assess the impact of lyophilization on the conformational and thermal stability of theresulting lyophilized vaccine, evaluated by biochemical and biophysical assays, and its efficacy will be assessedby functional immunogenicity in mice. This project will assess the feasibility of breaking the cold-chainrequirements for a next-generation particle vaccine system, which could be critical for resource-limited settings.In collaboration with the Texas Biomedical Research Institute (TBRI), a transgenic mouse model for SARS-CoV-2 infection will be used to study the thermostability on protection induced by the lyophilized, RBD particle vaccine.1 PROJECT NARRATIVE The rollout of FDA-authorized Pfizer (-80 ˚C storage) and Moderna (-20 ˚C storage) COVID-19 vaccines has highlighted the challenges posed by low requisite storage conditions, and elimination of cold chain requirements for emerging vaccine solutions would facilitate vaccine distribution and provide considerable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposes to investigate a lyophilization strategy for its vaccine adjuvant platform that induces spontaneous antigen particle formation. In this application, we will develop an optimized, thermostable lyophilized particle vaccine using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with a next-generation liposomal adjuvant. Antibodies ; Antigens ; immunogen ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biomedical Research ; Biophysics ; biophysical foundation ; biophysical principles ; biophysical sciences ; Biotechnology ; Biotech ; Cobalt ; cold temperature ; low temperature ; Cessation of life ; Death ; Economics ; Emergency Situation ; Emergencies ; Freeze Drying ; Freeze Dryings ; Lyophilization ; Freezing ; Human ; Modern Man ; Immunoglobulin G ; 7S Gamma Globulin ; IgG ; Immunization ; Immunologic Sensitization ; Immunologic Stimulation ; Immunological Sensitization ; Immunological Stimulation ; Immunostimulation ; Infection ; Lipid A ; Liposomes ; Liposomal ; Transgenic Mice ; Molecular Conformation ; Molecular Configuration ; Molecular Stereochemistry ; conformation ; conformational state ; Mus ; Mice ; Mice Mammals ; Murine ; Peer Review ; Phospholipids ; Phosphatides ; Porphyrins ; Protein Engineering ; genetic protein engineering ; protein design ; Research ; Research Institute ; Resources ; Research Resources ; Risk ; Sucrose ; Saccharose ; Temperature ; Testing ; Texas ; Trehalose ; United States Food and Drug Administration ; Food and Drug Administration ; USFDA ; Vaccines ; Virus Diseases ; Viral Diseases ; viral infection ; virus infection ; virus-induced disease ; aluminum sulfate ; Alum Adjuvant ; alum ; K-18 conjugate ; K-18 ; K18 ; K18 combination ; Measures ; Cost Savings ; base ; Clinical ; Phase ; Biological ; Biochemical ; QS21 ; QS 21 ; QS-21 Adjuvant ; Stimulon QS-21 Adjuvant ; Chemicals ; Serum ; Blood Serum ; Agonist ; Collaborations ; Cold Chains ; fluid ; liquid ; Liquid substance ; Intramuscular ; System ; neutralizing antibody ; high temperature ; High temperature of physical object ; particle ; receptor bound ; receptor binding ; thermolability ; thermostability ; develop a vaccine ; development of a vaccine ; vaccine formulation ; vaccine development ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Reporting ; social ; antigen bound ; antigen binding ; Molecular Interaction ; Binding ; Institution ; preventing ; prevent ; Homolog of Drosophila TOLL ; TLR4 ; Toll Homologue ; toll-like receptor 4 ; TLR4 gene ; Dose ; Data ; Recombinants ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Vaccine Adjuvant ; Adjuvant ; Authorization documentation ; Authorization ; Permission ; immunogenicity ; next generation ; nanoparticle ; nano particle ; nano-sized particle ; nanosized particle ; novel vaccines ; new vaccines ; next generation vaccines ; mouse model ; murine model ; reconstitution ; reconstitute ; vaccine candidate ; Antibody Response ; Formulation ; Immunize ; Inflammasome ; COVID-19 ; COVID19 ; CV-19 ; CV19 ; corona virus disease 2019 ; coronavirus disease 2019 ; 2019-nCoV ; 2019 novel corona virus ; 2019 novel coronavirus ; COVID-19 virus ; COVID19 virus ; CoV-2 ; CoV2 ; SARS corona virus 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 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 corona virus 2 ; Severe acute respiratory syndrome coronavirus 2 ; Severe acute respiratory syndrome related corona virus 2 ; Wuhan coronavirus ; coronavirus disease 2019 virus ; hCoV19 ; nCoV2 ; COVID-19 vaccine ; 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 ; 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 pandemic ; COVID crisis ; COVID epidemic ; COVID pandemic ; COVID-19 crisis ; COVID-19 epidemic ; COVID-19 global health crisis ; COVID-19 global pandemic ; COVID-19 health crisis ; COVID-19 public health crisis ; COVID19 crisis ; COVID19 epidemic ; COVID19 global health crisis ; COVID19 global pandemic ; COVID19 health crisis ; COVID19 pandemic ; COVID19 public health crisis ; SARS-CoV-2 epidemic ; SARS-CoV-2 global health crisis ; SARS-CoV-2 global pandemic ; SARS-CoV-2 pandemic ; SARS-CoV2 epidemic ; SARS-CoV2 pandemic ; SARS-coronavirus-2 epidemic ; SARS-coronavirus-2 pandemic ; Severe Acute Respiratory Syndrome CoV 2 epidemic ; Severe Acute Respiratory Syndrome CoV 2 pandemic ; Severe acute respiratory syndrome coronavirus 2 epidemic ; Severe acute respiratory syndrome coronavirus 2 pandemic ; corona virus disease 2019 epidemic ; corona virus disease 2019 pandemic ; coronavirus disease 2019 crisis ; coronavirus disease 2019 epidemic ; coronavirus disease 2019 global health crisis ; coronavirus disease 2019 global pandemic ; coronavirus disease 2019 health crisis ; coronavirus disease 2019 pandemic ; coronavirus disease 2019 public health crisis ; coronavirus disease crisis ; coronavirus disease epidemic ; coronavirus disease pandemic ; severe acute respiratory syndrome coronavirus 2 global health crisis ; severe acute respiratory syndrome coronavirus 2 global pandemic ; SARS-CoV-2 spike protein ; 2019-nCoV S protein ; 2019-nCoV spike glycoprotein ; 2019-nCoV spike protein ; COVID-19 S protein ; COVID-19 spike glycoprotein ; COVID-19 spike protein ; COVID19 S protein ; COVID19 spike glycoprotein ; COVID19 spike protein ; SARS-CoV-2 S protein ; SARS-CoV-2 spike glycoprotein ; SARS-CoV2 S protein ; SARS-CoV2 spike glycoprotein ; SARS-CoV2 spike protein ; Severe acute respiratory syndrome coronavirus 2 S protein ; Severe acute respiratory syndrome coronavirus 2 spike glycoprotein ; Severe acute respiratory syndrome coronavirus 2 spike protein ; coronavirus disease 2019 S protein ; coronavirus disease 2019 spike glycoprotein ; coronavirus disease 2019 spike protein ; vaccine distribution ; deploy vaccines ; distribute vaccines ; vaccine deployment ; vaccine roll-out ; vaccine rollout ; ACE2 ; angiotensin converting enzyme 2 ; angiotensin converting enzyme II ; SARS-CoV-2 infection ; COVID-19 infection ; COVID19 infection ; SARS-CoV2 infection ; Severe acute respiratory syndrome coronavirus 2 infection ; coronavirus disease 2019 infection ; 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 ; viral entry inhibitor ; block viral entry ; inhibit viral entry ; viral entry blocker ;

The coronavirus disease 2019 (COVID-19) global pandemic caused by Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2) is unprecedented in our lifetime and has caused major social, economic andhuman suffering. Globally, there have been 76,858,506 confirmed cases, leading to 1,711,498 deaths asreported by the WHO through December 2020. The rollout of FDA-authorized Pfizer (-80 ˚C storage) andModerna (-20 ˚C storage) vaccines has highlighted the challenges posed by low requisite storage temperatures.Elimination of cold chain requirements for emerging vaccine solutions could facilitate distribution and provideconsiderable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposesto investigate a lyophilization strategy for its novel vaccine adjuvant platform that induces spontaneous antigenparticles, using the receptor-binding domain (RBD) of the SARS CoV-2 spike (S) protein. We were amongst thefirst to show that a liquid form of RBD particles potently increases SARS-CoV-2 neutralizing antibodies by ordersof magnitude compared to the soluble antigen. Our vaccine platform induces the particle formation of well-characterized his-tagged antigens by simple admixing with liposomes that contain small amounts of cobaltporphyrin-phospholipid (CoPoP) and the clinical adjuvants monophosphoryl lipid A and QS-21. CoPoPliposomes give rise to rapid antigen particleization that is stable in biological media. In this collaborative Phase ISBIR proposal, we will assess the impact of lyophilization on the conformational and thermal stability of theresulting lyophilized vaccine, evaluated by biochemical and biophysical assays, and its efficacy will be assessedby functional immunogenicity in mice. This project will assess the feasibility of breaking the cold-chainrequirements for a next-generation particle vaccine system, which could be critical for resource-limited settings.In collaboration with the Texas Biomedical Research Institute (TBRI), a transgenic mouse model for SARS-CoV-2 infection will be used to study the thermostability on protection induced by the lyophilized, RBD particle vaccine.1

Public Health Relevance Statement:
PROJECT NARRATIVE The rollout of FDA-authorized Pfizer (-80 ˚C storage) and Moderna (-20 ˚C storage) COVID-19 vaccines has highlighted the challenges posed by low requisite storage conditions, and elimination of cold chain requirements for emerging vaccine solutions would facilitate vaccine distribution and provide considerable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposes to investigate a lyophilization strategy for its vaccine adjuvant platform that induces spontaneous antigen particle formation. In this application, we will develop an optimized, thermostable lyophilized particle vaccine using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with a next-generation liposomal adjuvant.

Project Terms:
<7S Gamma Globulin><2019-nCoV><2019 novel corona virus><2019 novel coronavirus><2019-nCoV vaccine><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein>