Approach to Strain Selection and the Propagation of Viral Stocks for Venezuelan Equine Encephalitis Virus Vaccine Efficacy Testing under the Animal Rule.
Abstract: Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical. An approach to selecting VEEV challenge strains for use under the Animal Rule was developed, taking into account Department of Defense (DOD) vaccine requirements, FDA Animal Rule guidelines, strain availability, and lessons learned from the generation of filovirus challenge agents within the Filovirus Animal Nonclinical Group (FANG). Initial down-selection to VEEV IAB and IC epizootic varieties was based on the DOD objective for vaccine protection in a bioterrorism event. The subsequent down-selection of VEEV IAB and IC isolates was based on isolate availability, origin, virulence, culture and animal passage history, known disease progression in animal models, relevancy to human disease, and ability to generate sufficient challenge material. Methods for the propagation of viral stocks (use of uncloned (wild-type), plaque-cloned, versus cDNA-cloned virus) to minimize variability in the potency of the resulting challenge materials were also reviewed. The presented processes for VEEV strain selection and the propagation of viral stocks may serve as a template for animal model development product testing under the Animal Rule to other viral vaccine programs. This manuscript is based on the culmination of work presented at the "Alphavirus Workshop" organized and hosted by the Joint Vaccine Acquisition Program (JVAP) on 15 December 2014 at Fort Detrick, Maryland, USA.
Publication Date: 2019-08-31 PubMed ID: 31480472PubMed Central: PMC6784384DOI: 10.3390/v11090807Google Scholar: Lookup
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Summary
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The research article outlines a procedure for selecting strains and propagating viral stocks of Venezuelan equine encephalitis virus (VEEV) for testing vaccine effectiveness, adhering to the FDA Animal Rule due to the unfeasibility and lack of ethics in carrying out human studies.
Venezuelan Equine Encephalitis Virus and the FDA Animal Rule
- The study focuses on Venezuelan equine encephalitis virus (VEEV), a virus that can have severe effects when aerosolized and thus needs an effective vaccine for protection. However, testing the effectiveness of such a vaccine in humans is neither feasible nor ethical.
- Due to these complications, the researchers used the U.S. Food and Drug Administration’s (FDA) Animal Rule to assess the vaccine’s efficacy. The Animal Rule allows for drug approval based on animal studies when it isn’t feasible or ethical to conduct human trials.
Research Approach
- The researchers developed an approach to select VEEV challenge strains for use under the Animal Rule, taking into account factors like the Department of Defense (DOD) vaccine requirements, FDA Animal Rule guidelines, availability of the strain, and valuable lessons derived from strain generation for the Filovirus Animal Nonclinical Group (FANG).
- Initially, they selected VEEV IAB and IC epizootic varieties based on DOD’s objective to protect against a bioterrorism event.
- Further down-selection of VEEV IAB and IC isolates was based on factors including availability, origin, virulence, culture and animal passage history, known disease progression in animal models, relevancy to human disease, and the ability to generate enough challenge material.
Propagation of Viral Stocks
- The researchers also examined the methods for the propagation of viral stocks. They compared the use of uncloned (wild-type) virus, plaque-cloned virus, and cDNA-cloned virus.
- The objective was to minimize variability in the potency of the resulting challenge materials.
Implication of the Study
- The established processes for VEEV strain selection and the propagation of viral stocks could potentially serve as a blueprint for animal model development and product testing within the framework of the Animal Rule for other viral vaccine programs.
- This work culminated in a presentation at the “Alphavirus Workshop” organized by the Joint Vaccine Acquisition Program (JVAP) on 15 December 2014, in Fort Detrick, Maryland, USA.
Cite This Article
APA
Rusnak JM, Glass PJ, Weaver SC, Sabourin CL, Glenn AM, Klimstra W, Badorrek CS, Nasar F, Ward LA.
(2019).
Approach to Strain Selection and the Propagation of Viral Stocks for Venezuelan Equine Encephalitis Virus Vaccine Efficacy Testing under the Animal Rule.
Viruses, 11(9), 807.
https://doi.org/10.3390/v11090807 Publication
Researcher Affiliations
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA. Janice.m.rusnak.ctr@mail.mil.
- Department of Virology, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702, USA.
- Institute for Human Infections and Immunity, World Reference Center for Emerging Viruses and Arboviruses and Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
- Battelle Biomedical Research Center, 1425 Plain City-Georgesville Road, West Jefferson, OH 43162, USA.
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA.
- Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA.
- Department of Virology, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, MD 21702, USA.
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA.
MeSH Terms
- Animals
- Disease Models, Animal
- Encephalitis Virus, Venezuelan Equine / genetics
- Encephalitis Virus, Venezuelan Equine / immunology
- Encephalitis Virus, Venezuelan Equine / pathogenicity
- Encephalomyelitis, Venezuelan Equine / prevention & control
- Encephalomyelitis, Venezuelan Equine / virology
- Guidelines as Topic
- Humans
- Immunization Programs / methods
- Immunization Programs / standards
- Viral Vaccines / therapeutic use
- Virology / methods
Conflict of Interest Statement
This work was co-written by employees of the U.S. Government (JR, AG, CB, LW, PG, and FN) as part of their official duties. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The authors declare no conflict of interest.
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