Intranasal nanoemulsion-adjuvanted HSV-2 subunit vaccine is effective as a prophylactic and therapeutic vaccine using the guinea pig model of genital herpes |
| |
| Affiliation: | 1. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;2. BlueWillow Biologics, Ann Arbor, MI, USA;3. University of Pennsylvania, Philadelphia, PA, USA;1. Laboratory of Biotechnology, Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan;2. Laboratory of Biotechnology, Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan;3. Laboratory of Biotechnology, Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan;4. Laboratory of Veterinary Parasitology, Nippon Veterinary and Life University, Musashino, Tokyo 180-8602, Japan;1. Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA;2. Acumen, LLC, Burlingame, CA, USA;3. Stanford University, Stanford, CA, USA;4. Centers for Medicare & Medicaid Services, Washington, DC, USA;1. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan;2. Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan;3. Medical Research Department, Mackay Memorial Hospital, New Taipei City, Taiwan;4. Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan;5. Department of Gastroenterology, Buddhist Tzu Chi General Hospital Taipei Branch, New Taipei City, Taiwan;1. Department of Epidemiology, Key Laboratory of Public Health Safety (Ministry of Education), Fudan University School of Public Health, Shanghai 200032, China;2. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA;3. Department of Internal Medicine, Division of Infectious Disease, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA;4. Department of Viral Hepatitis Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China;1. Department of Medical Laboratory Science, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana;2. Botswana National Health Laboratory, Gaborone, Botswana;3. Centers for Disease Control and Prevention, Atlanta, GA, USA;4. The Children''s Hospital of Philadelphia, USA;5. Botswana-UPenn Partnership, Gaborone, Botswana;6. Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana;7. WHO Regional Rotavirus Reference Laboratory, Diarrhoeal Pathogens Research Unit, Sefako Makgatho Health Sciences University, South Africa;8. WHO IST East and Southern Africa, Harare, Zimbabwe;9. McMaster University, Hamilton, Canada;10. African Rotavirus Surveillance Network, Immunization, Vaccines and Development Cluster, WHO African Regional Office, Brazzaville, Congo;11. University of British Columbia, Vancouver, Canada |
| |
| Abstract: | Genital herpes is a sexually transmitted disease representing a major global health concern. Currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. Herein, we describe an intranasal (IN) vaccine comprised of HSV-2 surface glycoproteins gD2 and gB2 formulated in a nanoemulsion adjuvant (NE01-gD2/gB2). Using the HSV-2 genital herpes guinea pig model, we demonstrate that IN NE01-gD2/gB2 induces higher levels of neutralizing antibody compared to a monovalent IN NE01-gD2 vaccine, but less than an intramuscular (IM) Alum/MPL-gD2 vaccine. Following intravaginal (IVag) challenge with HSV-2, the group immunized with IN NE01-gD2/gB2 exhibited significantly reduced acute and recurrent disease scores compared to placebo recipients. Significantly, latent virus was only detected in the dorsal root ganglia of 1 of 12 IN NE01-gD2/gB2-vaccinated animals compared to 11 of 12 placebo recipient. In the therapeutic model, IN NE01-gD2/gB2 immunized guinea pigs exhibited a significant reduction in the recurrent lesions scores (64%, p < 0.01), number of animal days with disease (64%, p < 0.01), number of animals with viral shedding (50%, p < 0.04) and reduction in virus positive vaginal swabs (56%, p < 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing virus transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and therapeutic vaccine against HSV-2. |
| |
| Keywords: | Herpes simplex virus type 2 Genital herpes Vaccine NanoVax Nanoemulsion |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
