Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA.
Oak Ridge Institute for Science and Education (ORISE), CDC Fellowship Program, Oak Ridge, TN, 37831, USA.
Adv Sci (Weinh). 2021 Aug;8(16):e2100693. doi: 10.1002/advs.202100693. Epub 2021 Jun 30.
Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen-specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections.
流感感染在全球范围内导致数百万人患上严重呼吸道疾病、住院和数十万人死亡。继发感染是流感高发病率和死亡率的主要原因,也是 1918 年、1968 年和 2009 年大流行严重程度的重要因素。此外,即使在流感季节,接种疫苗的个体也会出现其他呼吸道感染的发病率增加。研究了导致流感季节疫苗接种失败以及其他呼吸道感染的潜在机制。使用流感疫苗接种个体的外周血单核细胞 (PBMC) 来评估针对流感、麻疹和水痘的抗原特异性反应。从人类到小鼠模型的观察结果证实并扩展了该机制。流感病毒感染通过优先感染和杀死表达高水平唾液酸受体的活化淋巴细胞,从而抑制针对流感和其他呼吸道病原体的疫苗接种的持续适应性反应,即腺病毒和肺炎链球菌。这些发现提出了一个新的机制,即由于流感病毒感染,即使在免疫个体中,继发细菌和其他病毒以及流感和其他呼吸道病原体的疫苗接种失败导致继发呼吸道感染的高发病率。