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Principal Investigator: Shweta Kailasan
Organization: ABVACC, INC.
Fiscal Year: 2024
Award: $299,528
Funding agency: National Institute of Allergy and Infectious Diseases
There is an outbreak of Marburg virus disease (MVD), relative of Ebola virus, currently ongoing in Equatorial
Guinea and Tanzania. There have been multiple, deadly outbreaks of MVD in the past with ~88% lethality.
There are currently no approved vaccines or therapeutics for MVD and very few in clinical development. In
this proposal, we have rationally designed an immunogen based on MARV glycoprotein (GP) by excluding
domains known to trigger non-neutralizing antibodies allowing exposure of key neutralizing epitopes capable
of generating a strong immune response. Combined with a novel TLR7/8 agonist adjuvant, Alhydroxyquim-
II (AhQ-II), that has shown excellent safety and adjuvant activity in millions of people during COVID-19
pandemic, our rationally designed MARV vaccine induces broadly neutralizing antibodies against isolates
Angola, CI67, and Musoke strains of MARV as well as the phylogenetically more distant RAVV. Mice
immunized with this MARV vaccine with two or three doses compared to unadjuvanted antigen showed
robust antigen-specific binding and neutralizing titers against all four MARV strains demonstrated by ELISA
and pseudovirus neutralization assays. In the guinea pig model of MARV infection which shows all hallmarks
of filovirus disease the vaccine provided 100% protection against lethal challenge with no detectable viremia,
suggesting that the vaccine is likely inducing sterilizing immunity. In summary, this subunit vaccine represents
a novel, highly efficacious, and safe candidate for protection against MVD. Here, we propose three specific
aims to further develop this rationally designed immunogen: Aim1: To produce and generate a pooled stable
cell line for the MARV subunit antigen with a cGMP-compliant tag and demonstrate biochemical and
immunogenic properties comparable to the Streptavidin-tagged MARV material used in preliminary studies;
Aim 2: to determine optimal effective dose and regimen for maximum protection in BSL-4 guinea pig MARV
model; Aim 3: to demonstrate immunogenicity in the filovirus Gold Standard non-human primate model. Upon
successful completion of this Phase I project we anticipate a Phase II focused on NHP efficacy studies and
advanced development activities.
Terms: <Adjuvant><Advanced Development><Affinity><Africa><African><Agonist><Aman><Angola><Animals><Antibodies><Antibody titer measurement><Antigen-Antibody Complex><Antigenic Determinants><Antigens><Assay><BALB C Mouse><BALB/c><Binding><Binding Determinants><Bioassay><Biochemical><Biological Assay><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Case Fatality Rates><Cavia><Cell Body><Cells><Cessation of life><Clinical Treatment Moab><Crab-Eating Macaque><Crab-Eating Monkey><Cyclic GMP><Cynomolgus Monkey><Cynomolgus macaque><Death><Development><Disease><Disease Outbreaks><Disorder><Distant><Dose><EBOV><ELISA><Ebola><Ebola Hemorrhagic Fever><Ebola Virus Disease><Ebola disease><Ebola virus><Ebola-like Viruses><Engineering><Enzyme-Linked Immunosorbent Assay><Epitopes><Equatorial Guinea><Exclusion><Exhibits><Fatality rate><Filoviridae><Filoviridae Infections><Filovirus><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Frankfurt-Marburg Syndrome Virus><Ghana><Glycoproteins><Gold Coast><Grant><Guanosine Cyclic Monophosphate><Guinea Pigs><Guinea Pigs Mammals><Health Care Systems><Healthcare Systems><Human><Immune Complex><Immune response><Immunity><Immunization><Immunize><Immunological response><Immunology><In Vitro><Inbred BALB C Mice><Infection><Innate Immune Response><Knowledge><Life><M fascicularis><M. fascicularis><Macaca fascicularis><Marburg><Marburg Virus Disease><Marburg hemorrhagic fever><Marburg virus><Marburg-like Viruses><Marburgvirus><Medical><Medicine><Mice><Mice Mammals><Modeling><Modern Man><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><Outbreaks><Persons><Phase><Phylogenetic Analysis><Phylogenetics><Play><Point Mutation><Production><Property><Proteins><Quality Control><Recombinants><Regimen><Reporting><Research><Rodent><Rodentia><Rodents Mammals><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SBIR><Safety><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><Small Business Innovation Research><Small Business Innovation Research Grant><Spanish Guinea><Strepavidin><Streptavidin><Structural Biologist><Structure><Subunit Vaccines><T cell response><T-Cell Activation><TLR7><TLR7 gene><TLR8><TLR8 gene><Tanzania><Testing><Texas><Therapeutic><Time><Toll-Like Receptor 7><Toll-Like Receptor 8><Universities><Vaccine Adjuvant><Vaccine Design><Vaccines><Viremia><Virus><activate T cells><antibody titering><cGMP><clinical development><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><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><efficacy study><emergent outbreak><emerging outbreak><enzyme linked immunoassay><experience><filovirus infections><flow cytophotometry><guinea pig model><hemorrhagic fever virus><host response><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><in vivo><mAbs><monoclonal Abs><neutralizing antibody><new outbreak><non-human primate><nonhuman primate><novel><novel outbreak><pathogen><pre-clinical><preclinical><product development><protein purification><rational design><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sober><sobriety><social role><stable cell line><success><vaccine candidate><vaccine development><viraemia><viral disease outbreak><viral outbreak><viral sepsis><virus disease outbreak><virusemia>