CpG ODN G9.1 as a novel nasal ODN adjuvant elicits complete protection from influenza virus infection without causing inflammatory immune responses
CpG ODN G9.1 as a novel nasal ODN adjuvant elicits complete protection from influenza virus infection without causing inflammatory immune responses
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CpG ODN G9.1 作为一种新型鼻 ODN 佐剂，可完全保护免受流感病毒感染，且不会引起炎症免疫反应
DOI：
10.1016/j.vaccine.2019.07.032
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发表时间：
2019
期刊：
影响因子：
5.5
通讯作者：
Asanuma Hideki
中科院分区：
文献类型：
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作者：
Tateishi Koichiro;Fujihashi Kohtaro;Yamamoto Norio;Hasegawa Hideki;Ainai Akira;Sato Kayoko;Iho Sumiko;Yamamoto Saburo;Maeyama Jun-ichi;Odagiri Takato;Asanuma Hideki
本研究在局限于上呼吸道（URT）感染模型和下呼吸道（LRT）感染模型中，检测了鼻流感疫苗联合新型粘膜寡脱氧核苷酸（ODN）佐剂CpG ODN G9.1（G9.1）的保护效力和免疫应答。用A/加州/7/2009（Cal 7）裂解疫苗（X179 A）加G9.1经鼻致敏小鼠，然后用单独的X179 A经鼻给予加强免疫。当用大体积（LRT感染）或小体积（感染限于URT）活Cal 7流感病毒攻击小鼠时，经鼻给予G9.1联合X179 A的小鼠对仅限于URT的感染的保护率明显更高。此外，该组小鼠迅速从LRT感染中恢复。当小鼠皮下（s.c.）给予X179 A作为当前形式的疫苗接种，它们对仅限于URT的感染没有保护作用，但它们确实从LRT的感染中恢复。保护模式与流感病毒特异性粘膜分泌型伊加（SIgA）或血清IgG抗体（Ab）反应密切相关。因此，SIgA抗体应答在保护免受限于URT的感染中起重要作用，而流感病毒特异性血清IgG抗体应答有助于保护免受LRT的感染。值得注意的发现是，经鼻给予G9.1的小鼠的肺具有低水平的I型IFN相关蛋白和转录因子特异性mRNA表达。这些结果表明，鼻G9.1可用作流感疫苗的有效且安全的粘膜佐剂，因为该鼻疫苗系统激发粘膜SIgA和血清IgG Ab应答，其提供完全保护而不诱导有效的炎症应答。
This study examined the protective efficacy of and immune response to a nasal influenza vaccine combined with a novel mucosal oligodeoxynucleotide (ODN) adjuvant, CpG ODN G9.1 (G9.1), in a model of infection limited to the upper respiratory tract (URT) and a model of infection in the lower respiratory tract (LRT). Mice were nasally primed with an A/California/7/2009 (Cal7) split vaccine (X179A) plus G9.1 and were then nasally given a booster with X179A alone. When mice were challenged with either a large (infection of the LRT) or small (infection limited to the URT) volume of live Cal7 influenza virus, mice nasally given G9.1 combined with X179A had a markedly higher rate of protection against infection limited to the URT. Moreover, this group of mice promptly recovered from an infection of the LRT. When mice were subcutaneously (s.c.) given X179A as a current form of vaccination, they had no protection from an infection limited to the URT but they did recover from an infection of the LRT. The patterns of protection were closely correlated with influenza virus-specific mucosal secretory IgA (SIgA) or serum IgG antibody (Ab) responses. Thus, SIgA Abs responses play an important role in protection from an infection limited to the URT while influenza virus-specific serum IgG Ab responses help to protect from an infection of the LRT. A finding of note is that lungs from mice nasally given G9.1 had low levels of type I IFN-associated protein- and transcription factor-specific mRNA expression. These results suggest that nasal G9.1 can be used as an effective and safe mucosal adjuvant for influenza vaccines since this nasal vaccine system elicits both mucosal SIgA and serum IgG Ab responses that provide complete protection without inducing potent inflammatory responses.