R01AI160226

Preclinical development of a vaccine for Nipah virus - 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 (G) vesicular stomatitis virus (RVSVG) 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-randomized 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.

University Of Texas Medical Branch At Galveston

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Galveston, Texas 775555302 United States

Single Zip Code

Partnerships for Countermeasures against Select Pathogens (R01 Clinical Trials Not Allowed) (RFA-AI-20-028)

Amendment Since initial award the End Date has been extended from 02/28/26 to 02/28/27 and the total obligations have increased 247% from $1,415,990 to $4,912,518.