Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
PLoS One. 2009 Nov 12;4(11):e7790. doi: 10.1371/journal.pone.0007790.
Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.
自 2003 年以来，高致病性禽流感病毒 H5N1 亚型经常被报道引起人类感染，导致高发病率和死亡率。人们担心这些病毒会大流行，因此开发安全有效的疫苗是可取的。基于 MVA 的 H5N1 疫苗已经被证明在使用高剂量进行两次免疫时是有效的。当可生产的疫苗制剂数量有限时，剂量节约策略将增加可接种疫苗的人数。此外，保护性免疫在单次免疫后理想地诱导。因此，在小鼠中评估了基于 MVA 的 H5N1 疫苗诱导保护性免疫的最小要求。为此，用表达流感病毒 A/Vietnam/1194/04 的 HA 基因的重组 MVA 对小鼠进行一次或两次递减剂量的疫苗接种。通过评估体重减轻、病毒复制和组织病理学变化，确定了同源 clade 1 病毒和源自 clade 2.1 的异源病毒 A/Indonesia/5/05 攻毒感染后的保护效力。结论是，基于 MVA 的疫苗允许显著的剂量节约，并提供跨 clade 的保护，甚至在单次免疫后也是如此，这是 H5N1 疫苗候选物的有利特性。
