Belyakov Igor M, Earl Patricia, Dzutsev Amiran, Kuznetsov Vladimir A, Lemon Michael, Wyatt Linda S, Snyder James T, Ahlers Jeffrey D, Franchini Genoveffa, Moss Bernard, Berzofsky Jay A
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9458-63. doi: 10.1073/pnas.1233578100. Epub 2003 Jul 17.
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.
对天花生物恐怖主义的担忧引发了广泛接种疫苗的可能性，但如今免疫功能低下个体更为普遍，这就需要一种更安全的疫苗，而且保护机制尚未得到充分了解。我们在此表明，在足够剂量下，安卡拉痘苗病毒（modified vaccinia Ankara）和NYVAC复制缺陷痘苗病毒在免疫功能低下的动物中是安全的，它们提供的保护等同于已获许可的惠氏疫苗株针对致病性痘苗病毒鼻内攻击小鼠的保护作用。安卡拉痘苗病毒和惠氏病毒诱导的保护作用涉及相似的免疫反应种类和模式。对于两者而言，抗体对于预防疾病至关重要，而效应性CD4+和CD8+ T细胞既非必需也不充分。然而，在没有抗体的情况下，T细胞对于存活和恢复是必需且充分的。此外，T细胞在未免疫动物的亚致死性感染控制中发挥了更大作用。这些与现有天花疫苗共有的特性，为进一步评估这些复制缺陷痘苗病毒作为更安全的天花疫苗或预防痘苗病毒并发症的疫苗提供了依据。
