A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates
A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates
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DOI：
10.1128/cvi.00030-11
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发表时间：
2011-05-01
影响因子：
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通讯作者：
Schmaljohn, Connie S.
中科院分区：
文献类型：
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作者：
Dupuy, Lesley C.;Richards, Michelle J.;Schmaljohn, Connie S.
我们评估了表达委内瑞拉马脑炎病毒（VEEV）的密码子优化的包膜糖蛋白基因的DNA疫苗通过肌内电穿孔递送时的免疫原性和保护效力。用DNA疫苗接种的小鼠产生了与施用减毒活VEEV疫苗TC-83后观察到的相当的稳健的VEEV中和抗体应答，并且完全保护免于致命的气溶胶VEEV攻击。DNA疫苗还在兔中引起强烈的中和抗体应答，其在高水平下持续至少6个月，并且可以通过在初始疫苗接种后约6个月进行的DNA的单次额外电穿孔施用来加强。与阴性对照猕猴相比，通过肌内电穿孔接种疫苗的食蟹猴产生了大量中和抗体应答，气雾剂激发后未检测到血清病毒血症，发热反应、淋巴细胞减少症和疾病临床体征减少。综上所述，我们的结果表明，这种DNA疫苗提供了一种有效的手段，防止VEEV感染，并代表了一个有吸引力的候选人进一步发展。
We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development.