Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892-3005, USA.
Science. 2010 Aug 27;329(5995):1060-4. doi: 10.1126/science.1192517. Epub 2010 Jul 15.
The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for the development of a universal influenza vaccine for humans.
2009 年大流行性流感病毒的迅速传播凸显了需要通用流感疫苗来激发对多种病毒株的保护性免疫。在这里,我们表明,用编码 H1N1 流感血凝素 (HA) 的质粒 DNA 进行疫苗接种,并以季节性疫苗或复制缺陷型腺病毒 5 载体进行加强免疫,可刺激产生广泛中和流感的抗体。与单独使用任何一种成分相比,这种初次免疫/加强免疫组合增加了对可追溯至 1934 年至 2007 年的多种 H1N1 株的中和作用,并为小鼠和雪貂提供了针对不同 H1N1 病毒的保护。这些抗体针对 HA 的保守茎区,并且在非人类灵长类动物中也被诱导产生。该方法诱导的对 H1N1 亚型的交叉中和为开发人类通用流感疫苗提供了基础。