The proposal requests funding to support manufacturing and immune characterization of a novel, emulsifiedadjuvant which is uniquely compatible with lyophilization strategies to enable thermostabilization ofglycoprotein vaccines. The major objectives of the study are to transfer and optimize the manufacture of anovel adjuvant and to characterize and assess the comparative immunogenicity of different adjuvantformulations in terms of both humoral and cell mediated immunity, utilizing two different multimeric glycoproteinantigens. Ultimately, this program will identify an optimal adjuvant formulation, capable of potentiating bothhumoral and cell mediated immunity to protein antigens, compatible with lyophilization and resulting in athermostabilized vaccine utilizing Generally Regarded as Safe ("GRAS') excipients. Specific formulationdevelopment will be done in the context of the Zaire ebolavirus (EBOV) GP, a component of our trivalentfilovirus vaccine (TriFiloVax) targeting EBOV, Sudan ebolavirus (SUDV) and marburgvirus (MARV) and withSAR-CoV-2 spike protein, supporting COVID-19 vaccine development efforts. While state of the art medicaltreatment may increase the chances of survival of both the highly fatal EBOV and the highly transmissibleCOVID-19, currently no antiviral therapy is available to prevent or cure the disease. Vaccination remains themost feasible route for addressing and preventing future epidemics. Ongoing clinical development in thecontext of EBOV has identified both therapeutics and vaccines which are being tested in the ongoing outbreakin the Democratic Republic of Congo. However, these approaches are highly selective for EBOV only. The soleapproved vaccine is a virally vectored vaccine requiring cold storage (<-60°C) storage / distribution and alsocannot be used in at-risk populations showing any signs of immunodeficiency or in pregnant women and ispotentially more variable in less responsive populations. These vaccine platforms also may not be usedrepeatedly (either as boosters or with other protein antigens) because of the humoral induced immunity to theviral platform which occurs with vaccination. There is no vaccine for MARV, SUDV or COVID-19. In contrast,subunit vaccines offer many advantages, including improved safety, compatibility with immunosuppressed,immunocompromised or high risk populations or those who have previously received virally vectored vaccines.Thermostabilized formulations also facilitate stockpiling and emergency use in logistically challengingenvironments. The specific aims of the proposal include to i) transfer manufacturing methods and manufactureengineering lots of CoVaccine with varying Polysorbate 80 content and ii) characterize the enhancement ofboth humoral and cell mediated immunity by CoVaccine HT⢠with SARS-CoV-2 Spike protein and EBOV GP,thereby facilitating the development of TriFiloVax (for EBOV, MARV and SUDV) and CiVax (for COVID-19) andmore generally for other protein vaccines.
Public Health Relevance Statement: 8. Project Narrative Multimeric glycoprotein antigens are important potential vaccine candidates for both highly fatal and highly transmissible viral infections, including EBOV and COVID-19. Use of protein vaccines is considered one of the safest vaccine approaches but is limited by the ability to stimulate both humoral and cell mediated immunity. This proposal describes the immune characterization of a novel adjuvant, with the ability to stimulate both humoral and cell mediated immunity, and the potential to be an integral part of a thermostable glycoprotein vaccine platform with wide applicability to viral disease.
Project Terms: Elderly ; advanced age ; elders ; geriatric ; late life ; later life ; older adult ; older person ; senior citizen ; Antigens ; immunogen ; Awareness ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Transformed Cell Line ; Cells ; Cell Body ; Clinical Research ; Clinical Study ; Clinical Trials ; Cryopreservation ; Cryofixation ; cold preservation ; cold storage ; Cessation of life ; Death ; Disease ; Disorder ; Disease Outbreaks ; Outbreaks ; Ebola virus ; EBOV ; Ebola-like Viruses ; ebolavirus ; Emergency Situation ; Emergencies ; Engineering ; Environment ; Epidemic ; Excipients ; Family ; Flow Cytometry ; Flow Cytofluorometries ; Flow Cytofluorometry ; Flow Microfluorimetry ; Flow Microfluorometry ; flow cytophotometry ; Freeze Drying ; Freeze Dryings ; Lyophilization ; Future ; Glycoproteins ; glycosylation ; Metabolic Glycosylation ; Hawaii ; Viral Hemorrhagic Fevers ; hemorrhagic fever ; Human ; Modern Man ; Immunity ; Cellular Immunity ; Cell Mediated Immunology ; Cell-Mediated Immunity ; Humoral Immunities ; antibody-based immunity ; Immunologic Deficiency Syndromes ; Immunodeficiency Disorder ; Immunodeficiency Syndrome ; Immunological Deficiency Syndromes ; hypoimmunity ; immune deficiency disorder ; immunodeficiency ; Infection ; Insecta ; Insects ; Insects Invertebrates ; Joints ; Light ; Photoradiation ; Marburgvirus ; Frankfurt-Marburg Syndrome Virus ; Marburg ; Marburg virus ; Marburg-like Viruses ; Medical Staff ; Membrane Glycoproteins ; Cell Surface Glycoproteins ; Surface Glycoproteins ; Methods ; mortality ; Mus ; Mice ; Mice Mammals ; Murine ; Particle Size ; Polysorbate 80 ; Pregnant Women ; expectant mother ; expecting mother ; pregnant mothers ; Proteins ; Public Health ; Request for Proposals ; Research ; Risk ; Safety ; Testing ; Time ; Universities ; Vaccination ; Vaccines ; Virulence ; Virus Diseases ; Viral Diseases ; viral infection ; virus infection ; virus-induced disease ; Virus ; Work ; Democratic Republic of the Congo ; Belgian Congo ; Zaire ; aluminum sulfate ; Alum Adjuvant ; alum ; Immunocompromised Host ; Immunocompromised ; Immunocompromised Patient ; Immunosuppressed Host ; immunosuppressed patient ; Caregivers ; Care Givers ; Cavia ; Guinea Pigs ; Guinea Pigs Mammals ; Family member ; Mediating ; Caring ; improved ; Procedures ; Phase ; Medical ; Coronavirus ; Coronaviridae ; corona virus ; Filovirus ; Filoviridae ; nonhuman primate ; non-human primate ; Logistics ; Populations at Risk ; Filoviridae Infections ; filovirus infections ; Funding ; Antiviral Therapy ; anti-viral therapy ; viral infectious disease treatment ; Phase II Clinical Trials ; Phase 2 Clinical Trials ; phase II protocol ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; Therapeutic ; Attenuated ; programs ; Immunes ; Immune ; Route ; System ; antibody titering ; Antibody titer measurement ; neutralizing antibody ; Viral ; recombinant virus ; success ; thermolability ; thermostability ; develop a vaccine ; development of a vaccine ; vaccine formulation ; vaccine development ; plasmid vaccine ; vector vaccine ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Structure ; novel ; disorder model ; Disease model ; Property ; response ; Subunit Vaccines ; Early-Stage Clinical Trials ; Phase 1 Clinical Trials ; phase I protocol ; Phase I Clinical Trials ; GPI0100 ; GPI-0100 ; SUDV ; Sudan ebolavirus ; Sudan virus ; Sudan Ebola virus ; ZEBOV ; Zaire ebolavirus ; Zaire Ebola virus ; SARS Virus ; SARS corona virus ; SARS-Associated Coronavirus ; SARS-CoV ; SARS-Related Coronavirus ; Severe Acute Respiratory Syndrome Virus ; Severe Acute Respiratory Syndrome corona virus ; Severe Acute Respiratory Syndrome coronavirus ; severe acute respiratory syndrome-CoV ; SARS coronavirus ; preventing ; prevent ; cell mediated immune response ; Address ; Symptoms ; Recombinants ; Viral Vector ; Adjuvant ; Development ; developmental ; immunosuppressed ; immunogenicity ; cost effective ; Population ; Coupled ; comparative ; mouse model ; murine model ; vaccine candidate ; Middle East Respiratory Syndrome Coronavirus ; MERS corona virus ; MERS coronavirus ; MERS virus ; MERS-CoV ; Middle East Respiratory Syndrome Corona Virus ; Middle East Respiratory Syndrome Virus ; Middle East Respiratory Syndrome-CoV ; Middle Eastern Respiratory Syndrome Corona virus ; Middle Eastern Respiratory Syndrome Coronavirus ; Middle Eastern Respiratory Syndrome Virus ; Middle Eastern Respiratory Syndrome-CoV ; Zika Virus ; ZIKV ; zikav ; Formulation ; high risk population ; high risk group ; clinical development ; Immunize ; medical countermeasure ; 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 ; 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 ;
