Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
Virus Res. 2013 Dec 5;178(1):78-98. doi: 10.1016/j.virusres.2013.05.006. Epub 2013 May 28.
The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting.
自 1997 年以来，高致病性禽流感 H5N1 病毒的传播及其对家禽和人类的毒力引起了人们对其引发流感大流行的潜在威胁的关注。疫苗是应对大流行威胁最可行的手段。然而，如果大流行迅速传播，生产、分发和实施新疫苗将是一项挑战。因此，人们正在努力开发使用较少抗原并能诱导交叉保护和持久反应的大流行疫苗，这些疫苗可以在大流行宣布时甚至可能在之前就进行接种，以使人群得到免疫，并允许迅速产生保护性抗体反应。在过去几年中，几家疫苗制造商已经基于反向遗传学开发了候选大流行和大流行前疫苗，并通过使用不同佐剂对这些疫苗进行配方改进，提高了其免疫原性。从 H5N1 疫苗的临床研究中得到了一些重要且一致的观察结果：通常需要接种两剂灭活疫苗才能达到符合许可标准所需的免疫水平，如果包含油包水佐剂，则可以使用较少的抗原，一般来说，抗体滴度迅速下降，但可以通过额外剂量的疫苗进行加强，如果产生了高滴度的抗体，则会观察到对其他谱系的交叉反应。初次免疫和加强免疫策略会引发更强大的免疫反应。在这篇综述中，我们讨论了各种 H5N1 流感疫苗的临床试验数据。我们还描述了在动物模型中进行的研究，以探讨大流行减毒活疫苗候选物与季节性流感病毒之间发生重配的可能性，因为这是在大流行情况下使用活疫苗的一个重要考虑因素。
