Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2476-81. doi: 10.1073/pnas.1323954111. Epub 2014 Jan 27.
The 2009 H1N1 pandemic and recent human cases of H5N1, H7N9, and H6N1 in Asia highlight the need for a universal influenza vaccine that can provide cross-strain or even cross-subtype protection. Here, we show that recombinant monoglycosylated hemagglutinin (HAmg) with an intact protein structure from either seasonal or pandemic H1N1 can be used as a vaccine for cross-strain protection against various H1N1 viruses in circulation from 1933 to 2009 in mice and ferrets. In the HAmg vaccine, highly conserved sequences that were originally covered by glycans in the fully glycosylated HA (HAfg) are exposed and thus, are better engulfed by dendritic cells (DCs), stimulated better DC maturation, and induced more CD8+ memory T cells and IgG-secreting plasma cells. Single B-cell RT-PCR followed by sequence analysis revealed that the HAmg vaccine activated more diverse B-cell repertoires than the HAfg vaccine and produced antibodies with cross-strain binding ability. In summary, the HAmg vaccine elicits cross-strain immune responses that may mitigate the current need for yearly reformulation of strain-specific inactivated vaccines. This strategy may also map a new direction for universal vaccine design.
2009 年 H1N1 大流行和亚洲近期发生的 H5N1、H7N9 和 H6N1 人间病例突显了需要一种通用流感疫苗，该疫苗能够提供针对不同毒株甚至不同亚型的保护。在这里，我们展示了具有完整蛋白结构的重组单糖基化血凝素（HAmg）可作为疫苗，针对来自 1933 年至 2009 年在小鼠和雪貂中流行的各种 H1N1 病毒提供针对不同毒株的保护。在 HAmg 疫苗中，高度保守的序列最初被完全糖基化 HA（HAfg）中的聚糖覆盖，现在暴露出来，因此，更容易被树突状细胞（DC）吞噬，刺激更好的 DC 成熟，并诱导更多的 CD8+记忆 T 细胞和分泌 IgG 的浆细胞。通过单细胞 RT-PCR 进行序列分析后发现，HAmg 疫苗比 HAfg 疫苗激活了更多样的 B 细胞库，并产生了具有不同毒株结合能力的抗体。综上所述，HAmg 疫苗可引发针对不同毒株的免疫反应，可能缓解目前对每年针对特定毒株的灭活疫苗进行重新配方的需求。该策略还可能为通用疫苗设计开辟新的方向。
