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Principal Investigator: Thomas William Geisbert
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2021
Award: $1,415,990
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high
as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed
vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen
because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and
the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is
also categorized as a Category C priority pathogen by several US Government agencies because of the concern
for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018
List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened
concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC
recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures
have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective
prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with
laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ΔG) vesicular
stomatitis virus (rVSVΔG) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses
have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses.
In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated
in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This
vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed
replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that
these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when
used as single injection vaccines. This new data is critically important in the context of containing outbreaks as
the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that
works rapidly with a single administration. Development of a replication restricted platform that provides improved
safety without compromising efficacy is a highly significant advancement and can be applied to other viruses
with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV
(rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and
pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard
to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank
(RVB), a manufacturing process, and conduct of GLP-safety toxicology.
Terms: <Advanced Development><Aman><Animals><Assay><Awareness><Bangladesh><Bioassay><Biologic Assays><Biologic Therapy><Biological Assay><Biological Markers><Biological Response Modifier Therapy><Biological Therapy><Biotech><Biotechnology><Brain Inflammation><CDC><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 pandemic><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><Case Fatality Rates><Category C pathogen><Category C priority pathogen><Cell Body><Cells><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Cluster randomization trial><Cluster randomized trial><Collaborations><Complement><Complement Proteins><Containment><Data><Development><Development and Research><Disease><Disease Outbreaks><Disorder><Domestic Rabbit><Dose><Drugs><EBOV><Ebola><Ebola Hemorrhagic Fever><Ebola Virus Disease><Ebola disease><Ebola virus><Ebola-like Viruses><Effectiveness><Encephalitis><Epidemic><European Community><European Union><Fatality rate><Federation of Malaya><Fever><Food and Drug Administration><Frankfurt-Marburg Syndrome Virus><French Guinea><Funding><G-Proteins><GTP-Binding Proteins><GTP-Regulatory Proteins><Glycoproteins><Government Agencies><Guanine Nucleotide Coupling Protein><Guanine Nucleotide Regulatory Proteins><Guinea><Health Care Providers><Health Personnel><Healthcare Providers><Healthcare worker><Henipavirus><History><Human><Human Resources><Immunity><India><Infection><Injections><Investigators><Laboratories><Lassa fever virus><Lassa virus><Lead><Lung diseases><Malay Federation><Malaya><Malaysia><Mammalia><Mammals><Manpower><Marburg><Marburg virus><Marburg-like Viruses><Marburgvirus><Medication><Methods><Mice><Mice Mammals><Modern Man><Morbidity><Morbidity - disease rate><Murine><Mus><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Nature><Nervous System Diseases><Neurologic Disorders><Neurological Disorders><Nipah Virus><Oryctolagus cuniculus><Outbreaks><Pathogenicity><Pathologic><Pb element><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Position><Positioning Attribute><Preventative vaccine><Preventive vaccine><Process><Prophylactic vaccine><Publications><Pulmonary Diseases><Pulmonary Disorder><Pyrexia><R & D><R&D><Rabbits><Rabbits Mammals><Recombinant Vaccines><Recombinants><Recording of previous events><Regulatory Affairs><Reporting><Research><Research Personnel><Researchers><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><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><Safety><Scientific Publication><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><Singapore><Stomatitis><Toxicology><Transmission><USFDA><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><United States Food and Drug Administration><United States National Institutes of Health><VSV><Vaccination><Vaccines><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral Diseases><Viral Vaccines><Virus><Virus Diseases><Work><World Health Organization><Zoonoses><Zoonotic><Zoonotic Infection><animal rule><base><bio-markers><biologic marker><biological therapeutic><biological treatment><biomarker><biotherapeutics><biotherapy><cell bank><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><develop a vaccine><development of a vaccine><developmental><disease of the lung><disorder of the lung><drug/agent><ebolavirus><evaluate vaccines><experience><febrile><febris><health care personnel><health care worker><health provider><health workforce><healthcare personnel><heavy metal Pb><heavy metal lead><improved><lung disorder><lung pathogen><manufacturing process><medical countermeasure><medical personnel><meetings><mortality><nervous system disorder><neurological disease><neuron toxicity><neuronal toxicity><neurotoxicity><non-human primate><nonhuman primate><open label><open label study><pandemic><pandemic disease><pathogen><personnel><phase 1 trial><phase I trial><plasmid vaccine><pre-clinical development><preclinical development><prevent><preventing><priority pathogen><product development><programs><pulmonary pathogen><research and development><respiratory pathogen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><transmission process><treatment provider><vaccine antibodies><vaccine development><vaccine evaluation><vaccine formulation><vaccine induced antibodies><vaccine safety><vaccine screening><vaccine testing><vaccine-induced antibodies><vector vaccine><viral infection><virus infection><virus-induced disease>