Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses
Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses
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DOI：
10.1073/pnas.1233578100
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发表时间：
2003-08-05
影响因子：
11.1
通讯作者：
Berzofsky, JA
中科院分区：
文献类型：
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作者：
Belyakov, IM;Earl, P;Berzofsky, JA
对天花生物恐怖主义的担忧提高了广泛接种疫苗的可能性，但今天免疫功能低下的个体更普遍，需要更安全的疫苗，并且保护机制尚未得到很好的理解。在这里，我们表明，在足够的剂量下，由改良的安卡拉牛痘病毒和NYVAC复制缺陷型牛痘病毒提供的保护，在免疫功能低下的动物中是安全的，相当于授权的惠氏疫苗株对小鼠的致病性牛痘病毒鼻内攻击。一个类似的品种和模式的免疫反应，参与了保护诱导的修饰牛痘安卡拉和惠氏病毒。对于这两种情况，抗体是预防疾病所必需的，而效应CD4（+）和CD8（+）T细胞都不是必需或足够的。然而，在缺乏抗体的情况下，T细胞是生存和恢复所必需的。此外，T细胞在控制未免疫动物的亚致死感染方面发挥了更大的作用。这些特性与现有的天花疫苗相同，为进一步评价这些复制缺陷型牛痘病毒作为对抗天花或牛痘病毒并发症的更安全疫苗提供了基础。
The concern about bioterrorism with smallpox has raised the possibility of widespread vaccination, but the greater prevalence of immunocompromised individuals today requires a safer vaccine, and the mechanisms of protection are not well understood. Here we show that, at sufficient doses, the protection provided by both modified vaccinia Ankara and NYVAC replication-deficient vaccinia viruses, safe in immunocompromised animals, was equivalent to that of the licensed Wyeth vaccine strain against a pathogenic vaccinia virus intranasal challenge of mice. A similar variety and pattern of immune responses were involved in protection induced by modified vaccinia Ankara and Wyeth viruses. For both, antibody was essential to protect against disease, whereas neither effector CD4(+) nor CD8(+) T cells were necessary or sufficient. However, in the absence of antibody, T cells were necessary and sufficient for survival and recovery. Also, T cells played a greater role in control of sublethal infection in unimmunized animals. These properties, shared with the existing smallpox vaccine, provide a basis for further evaluation of these replication-deficient vaccinia viruses as safer vaccines against smallpox or against complications from vaccinia virus.