Vaccine R&D, Baxter BioScience, Biomedical Research Centre, Uferstraße 15, A-2304 Orth/Donau, Austria.
Vaccine. 2012 Aug 10;30(37):5533-40. doi: 10.1016/j.vaccine.2012.06.043. Epub 2012 Jun 29.
Preparation for an H5N1 influenza pandemic in humans could include priming the population in the pre-pandemic period with a vaccine produced from an existing H5N1 vaccine strain, with the possibility of boosting with a pandemic virus vaccine when it becomes available. We investigated the longevity of the immune response after one or two priming immunizations with a whole-virus H5N1 vaccine and the extent to which this can be boosted by later immunization with either a homologous or heterologous vaccine.
Mice received one or two priming immunizations with a Vero cell culture-derived, whole-virus clade 1 H5N1 vaccine formulated to contain either 750 ng or 30 ng hemagglutinin. Six months after the first priming immunization, mice received either a booster immunization with the same clade 1 vaccine or a heterologous clade 2.1 vaccine, or buffer. Humoral and cellular immune responses were evaluated before and at regular intervals after immunizations. Three weeks after booster immunization, mice were challenged with a lethal dose of wild-type H5N1 virus from clades 1, 2.1 or 2.2 and survival was monitored for 14 days.
One or two priming immunizations with the 750 ng or 30 ng HA formulations, respectively, induced H5N1-neutralizing antibody titers which were maintained for ≥ 6 months and provided long-term cross-clade protection against wild-type virus challenge. Both humoral and cellular immune responses were substantially increased by a booster immunization after 6 months. The broadest protective immunity was provided by an immunization regimen consisting of one or two priming immunizations with a clade 1 vaccine and a boosting immunization with a clade 2.1 vaccine.
These data support the concept that pre-pandemic vaccination can provide robust and long-lasting H5N1 immunity which could be effectively boosted by immunization either with another pre-pandemic vaccine or with the pandemic strain vaccine.
人类 H5N1 流感大流行的准备工作可能包括在大流行前用现有 H5N1 疫苗株生产的疫苗对人群进行接种，当大流行病毒疫苗可用时，有可能用该疫苗进行加强免疫。我们研究了一次或两次接种全病毒 H5N1 疫苗后的免疫反应的持久性，以及通过后来接种同源或异源疫苗可以在多大程度上增强这种免疫反应。
小鼠接受了一次或两次用 Vero 细胞培养衍生的、含有 750ng 或 30ng 血凝素的全病毒 clade 1 H5N1 疫苗进行的初免免疫。初次免疫接种 6 个月后，小鼠接受了相同 clade 1 疫苗或异源 clade 2.1 疫苗的加强免疫接种，或缓冲液。在免疫前后定期评估体液和细胞免疫反应。加强免疫接种后 3 周，用来自 clade 1、2.1 或 2.2 的野生型 H5N1 病毒进行致死剂量的攻毒，监测 14 天的存活情况。
分别用 750ng 或 30ng HA 制剂进行一次或两次初免免疫，可诱导出 H5N1 中和抗体滴度，该滴度可维持至少 6 个月，并对野生型病毒攻击提供长期的跨 clade 保护。6 个月后加强免疫接种可显著增强体液和细胞免疫反应。由 clade 1 疫苗进行一次或两次初免免疫和用 clade 2.1 疫苗进行加强免疫的免疫方案可提供最广泛的保护免疫。
这些数据支持这样一种概念，即大流行前接种疫苗可以提供强大且持久的 H5N1 免疫力，通过用另一种大流行前疫苗或大流行株疫苗进行免疫接种，可以有效地增强这种免疫力。
