School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, USA.
Sci Rep. 2017 Nov 2;7(1):14912. doi: 10.1038/s41598-017-14891-y.
Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010-2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10-100 MLD of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 10 virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within the HA subtypes and protected 100% of mice from 8 of 9 lethal heterologous influenza virus challenges. The vaccine protection was dose dependent, in general, and a dose as low as 5 × 10 vp/mouse still provided 100% survival against 7 of 9 lethal heterologous influenza challenges. These data indicate that very low doses of Adenovirus-vectored consensus vaccines induce superior levels of immunity against a wide divergence of influenza subtypes as compared to traditional vaccines. These doses are scalable and translatable to humans and may provide the foundation for complete and long-lasting anti-influenza immunity.
将表达 H1-con、H2-con、H3-con 和 H5-con 血凝素共识基因的腺病毒组合（多价）免疫小鼠，并与用传统的 2010-2011 年 FluZone 和 FluMist 季节性疫苗免疫的小鼠进行比较。免疫后的小鼠用 10-100 MLD 的 H1N1、H3N1、H3N2 和 H5N1 流感病毒进行攻毒。传统疫苗诱导了强大的血凝素抑制（HI）滴度，但未能预防 5 种不同的异源致死性流感挑战。相反，多价共识疫苗（1×10 病毒颗粒（vp）/只）诱导了针对 10 种流感病毒中的 8 种的保护性 HI 滴度≥40，这些病毒在血凝素亚型内具有广泛的差异，并保护 100%的小鼠免受 9 种致死性异源流感病毒挑战的侵害。疫苗保护作用通常呈剂量依赖性，低至 5×10 vp/只的剂量仍能提供 100%的存活率，以抵抗 9 种致死性异源流感挑战中的 7 种。这些数据表明，与传统疫苗相比，腺病毒载体共识疫苗的非常低剂量可诱导针对广泛流感亚型的更高水平的免疫。这些剂量是可扩展和可转化为人类的，可能为完全和持久的抗流感免疫提供基础。
