Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus
Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus
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DOI：
10.1073/pnas.0804985105
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发表时间：
2008-08-05
影响因子：
11.1
通讯作者：
Moss, Bernard
中科院分区：
文献类型：
--
作者：
Earl, Patricia L.;Americo, Jeffrey L.;Moss, Bernard
30年前，世界卫生组织根除天花计划的成功导致常规疫苗接种的终止，从而导致人群免疫力下降。尽管人们对天花的重新引入感到关切，但由于医学禁忌症和预期的严重副作用，人们对大规模重新部署许可的活牛痘病毒疫苗没有什么热情。因此，高度减毒的毒株，如改良的安卡拉牛痘病毒（MVA）正在人类和动物模型中进行评估。先前的研究表明，用MVA引发和加强在猴痘病毒攻击模型中提供> 2年的保护。然而，如果天花病毒被用作生物武器，疫苗迅速诱导免疫的能力将是必不可少的。在这里，我们证明了与许可的Dryvax疫苗相比，MVA单次接种后更快速的免疫应答。为了确定两种疫苗的保护动力学，在免疫后4、6、10和30天用猴痘病毒静脉内攻击猕猴。在接种MVA或Dryvax后6天或更长时间，猴在临床上受到保护（接种MVA的16只动物中的1只除外），尽管MVA接种组的病毒载量和皮肤病变数量通常较高。然而，在免疫和静脉内攻击之间只有4天，MVA仍然保护，而Dryvax失败。与Dryvax相比，保护作用与对MVA更快的免疫应答相关，这可能与可以安全耐受的更高剂量的MVA有关。
The success of the World Health Organization smallpox eradication program three decades ago resulted in termination of routine vaccination and consequent decline in population immunity. Despite concerns regarding the reintroduction of smallpox, there is little enthusiasm for large-scale redeployment of licensed live vaccinia virus vaccines because of medical contraindications and anticipated serious side effects. Therefore, highly attenuated strains such as modified vaccinia virus Ankara (MVA) are under evaluation in humans and animal models. Previous studies showed that priming and boosting with MVA provided protection for > 2 years in a monkeypox virus challenge model. If variola virus were used as a biological weapon, however, the ability of a vaccine to quickly induce immunity would be essential. Here, we demonstrate more rapid immune responses after a single vaccination with MVA compared to the licensed Dryvax vaccine. To determine the kinetics of protection of the two vaccines, macaques were challenged intravenously with monkeypox virus at 4, 6, 10, and 30 days after immunization. At 6 or more days after vaccination with MVA or Dryvax, the monkeys were clinically protected (except for 1 of 16 animals vaccinated with MVA), although viral loads and number of skin lesions were generally higher in the MVA vaccinated group. With only 4 days between immunization and intravenous challenge, however, MVA still protected whereas Dryvax failed. Protection correlated with the more rapid immune response to MVA compared to Dryvax, which may be related to the higher dose of MVA that can be tolerated safely.