Vaccine Research and Development, Baxter BioScience, Orth/Donau, Austria.
PLoS One. 2011;6(8):e23791. doi: 10.1371/journal.pone.0023791. Epub 2011 Aug 18.
Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge.
We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus.
Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species.
These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.
基于vero 细胞培养的全病毒 H5N1 疫苗已在临床试验中广泛测试，结果一致显示其安全且具有免疫原性；然而，在没有广泛人类疾病的情况下，很难评估其临床疗效。目前已经建立了一种致死性小鼠模型，可用于研究主动免疫接种或被动转移疫苗诱导的血清在致死性 H5N1 攻击后的保护效果。
我们使用被动转移免疫血清来研究基于 vero 细胞培养的、无佐剂的灭活全病毒 H5N1 疫苗所引起的抗体介导的保护作用。小鼠通过静脉注射 H5N1 疫苗诱导的啮齿动物或人类免疫血清，随后用致死剂量的野生型 H5N1 病毒进行攻击。
被动转移 H5N1 疫苗诱导的小鼠、豚鼠和人免疫血清为受体小鼠提供了针对野生型 H5N1 病毒致死性攻击的剂量依赖性保护。所有免疫血清的血清 H5N1 中和抗体滴度的保护剂量 50 值均计算为≤1∶11，与来源物种无关。
这些数据为基于 vero 细胞培养的全病毒 H5N1 疫苗在大流行情况下将有效的信心提供了依据，并支持使用中和血清抗体滴度作为 H5N1 疫苗保护的相关性指标。
