- Introduction
- Materials and Methods
- Results
- Safety of RepliVAX WN vaccination in non-human primates.
- Induction of WNV-specific IgM and IgG responses by one dose of RepliVAX WN.
- Increased antibody titers in animals given booster immunizations with a second dose of RepliVAX WN.
- Protection of rhesus macaques from WNV viremia by one or two immunizations with RepliVAX WN.
- Analyses of cellular responses to RepliVAX WN vaccination and WNV infection.
- Discussion
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Evaluation of RepliVAX WN, a Single-Cycle Flavivirus Vaccine, in a Non-Human Primate Model of West Nile Virus Infection
West Nile virus (WNV) causes serious neurologic disease, but no licensed vaccines are available to prevent this disease in humans. We have developed RepliVAX WN, a single-cycle flavivirus with an expected safety profile superior to other types of live-attenuated viral vaccines. In this report we describe studies examining RepliVAX WN safety, potency, and efficacy in a non-human primate model of WNV infection. A single immunization of four rhesus macaques with RepliVAX WN was safe and elicited detectable neutralizing antibody titers and IgM and IgG responses, and IgG titers were increased in two animals that received a second immunization. After challenge with WNV, three of four immunized animals were completely protected from viremia, and the remaining animal showed minimal viremia on one day. In contrast, the unvaccinated animal developed viremia that lasted six days. These results demonstrate the efficacy and safety of RepliVAX WN in this primate model of WNV infection.
Author Notes
Disclosure: P. Mason is an inventor on the patents filed for RepliVAX technology. This statement is made in the interest of full disclosure and not because the author considers this a conflict of interest.
Financial support: This study was supported by a grant from the National Institute of Allergy and Infectious Diseases to Peter W. Mason and the Nonhuman Primate Core through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (National Institutes of Health [NIH] grant U54 AI057156). Douglas G. Widman was supported by a James W. McLaughlin fellowship. Amelia P. Travassos Da Rosa and Robert B. Tesh were supported in part by NIH contract NO1-AI30027. Luis D. Giavedoni and Vida L. Hodara were supported by NIH grants R51 RR13566 and R24 RR023345.
Authors' addresses: Douglas G. Widman, Department of Microbiology and Immunology, 3.218 Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX (current address: Lineberger Comprehensive Cancer Center; University of North Carolina, CB7295, Chapel Hill, NC, E-mail: dgwidman@med.unc.edu). Tomohiro Ishikawa, Department of Microbiology and Immunology, 3.218 Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX (current address: Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan, E-mail: toishika@port.kobe-u.ac.jp). Luis D. Giavedoni, Vida L. Hodara, Jean L. Patterson, and Ricardo Carrion Jr, Southwest National Primate Research Center and Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX, E-mails: lgiavedo@sfbr.org, vhodara@sfbr.org, jpatterson@sfbr.org, and carrion@sfbr.org. Melissa de la Garza, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, E-mail: mdelagar@sfbr.org. Jessica A. Montalbo, Veterinary Food Analysis and Diagnostic Laboratory, Department of Defense, Fort Sam Houston, TX, E-mail: jessica.montalbo@us.army.mil. Amelia P. Travassos Da Rosa, Department of Pathology, 4.104 Keiller Building, University of Texas Medical Branch, Galveston, TX, E-mail: aptravas@utmb.edu. Robert B. Tesh, Department of Microbiology and Immunology, and Department of Pathology, 3.146 Keiller Building, University of Texas Medical Branch, Galveston, TX, E-mail: rtesh@utmb.edu. Nigel Bourne, Departments of Microbiology and Immunology, Pathology, Pediatrics, and Sealy Center for Vaccine Development, 3.206C Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX, E-mail: nibourne@utmb.edu. Peter W. Mason, Department of Microbiology and Immunology, and Department of Pathology, 3.206B Mary Moody Northen Pavilion, University of Texas Medical Branch, Galveston, TX, E-mail: pwmason@utmb.edu (current address: Microbial Molecular Biology, Novartis Vaccines and Diagnostics, Cambridge, MA, E-mail: peter.mason@novartis.com).