Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, NIAID, NIH, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Vaccine. 2018 Mar 27;36(14):1871-1879. doi: 10.1016/j.vaccine.2018.02.061. Epub 2018 Mar 1.
The continued detection of zoonotic influenza infections, most notably due to the avian influenza A H5N1 and H7N9 subtypes, underscores the need for pandemic preparedness. Decades of experience with live attenuated influenza vaccines (LAIVs) for the control of seasonal influenza support the safety and effectiveness of this vaccine platform. All LAIV candidates are derived from one of two licensed master donor viruses (MDVs), cold-adapted (ca) A/Ann Arbor/6/60 or ca A/Leningrad/134/17/57. A number of LAIV candidates targeting avian H5 influenza viruses derived with each MDV have been evaluated in humans, but have differed in their infectivity and immunogenicity. To understand these differences, we generated four H5N2 candidate pandemic LAIVs (pLAIVs) derived from either MDV and compared their biological characteristics in vitro and in vivo. We demonstrate that all candidate pLAIVs, regardless of gene constellation and derivation, were comparable with respect to infectivity, immunogenicity, and protection from challenge in the ferret model of influenza. These observations suggest that differences in clinical performance of H5 pLAIVs may be due to factors other than inherent biological properties of the two MDVs.
持续检测到动物源流感感染，尤其是由于甲型流感 H5N1 和 H7N9 亚型，突显了大流行防范的必要性。几十年来，使用减毒活流感疫苗（LAIV）控制季节性流感的经验支持了这种疫苗平台的安全性和有效性。所有 LAIV 候选物均源自两种许可的主供体病毒（MDV）之一，即冷适应（ca）A/Ann Arbor/6/60 或 ca A/Leningrad/134/17/57。已经在人类中评估了针对禽源 H5 流感病毒的许多使用每种 MDV 衍生的 LAIV 候选物，但它们在感染力和免疫原性方面存在差异。为了了解这些差异，我们生成了源自 MDV 的四种 H5N2 候选大流行 LAIV（pLAIV），并比较了它们在体外和体内的生物学特性。我们证明，所有候选 pLAIV 无论基因构成如何，在感染性、免疫原性以及在雪貂流感模型中的保护作用方面均具有可比性。这些观察结果表明，H5 pLAIV 的临床性能差异可能归因于两种 MDV 的固有生物学特性以外的因素。
