A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation |
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| Institution: | 1. Ichor Medical Systems, Inc., San Diego, CA, USA;2. United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA;1. Inviragen, Inc., Madison, WI, USA;2. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA;3. Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA;4. Inviragen, Inc., Ft Collins, CO, USA;1. School of Public Health, Medical Science Center, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China;2. Scientific Affairs, Pfizer Vaccines Europe, 23-25 Avenue du Dr. Lannelongue, F-75014 Paris, France;3. Medicines and Scientific Vaccines Division, Pfizer Investment Co., Ltd., 36/F, CITIC Square, 1168 Nan Jing Road (W), Shanghai 200041, PR China;4. Pfizer Investment Co., Ltd., The Fifth Square, Tower B, 9/F, No. 3-7, Chaoyangmen North Avenue, Dongcheng District, Beijing 100010, PR China;1. AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong SAR, PR China;2. HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People''s Hospital, Guangdong Medical College, Shenzhen, PR China;3. Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PR China;1. CICS-UBI – Health Science Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal;2. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad 500078, Telangana, India;3. The University of Texas at Austin, College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, Austin, TX 78712, USA;1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;2. Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;3. Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;4. Department of Medicine, Division of Infectious Diseases, Hope Clinic of the Emory Vaccine Center, Emory School of Medicine, Decatur, GA, USA;5. University of Maryland Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA |
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| Abstract: | Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid? Delivery System. Subjects in IM-EP groups received 0.5 mg (N = 8) or 2.0 mg (N = 9) of pWRG/VEE or a saline placebo (N = 4) in a 1.0 ml injection. Subjects in ID-EP groups received 0.08 mg (N = 8) or 0.3 mg (N = 8) of DNA or a saline placebo (N = 4) in a 0.15 ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels.Clinicaltrials.gov registry number NCT01984983. |
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| Keywords: | Venezuelan equine encephalitis DNA vaccine Electroporation Intramuscular Intradermal Human Clinical trial Phase 1 |
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