Jirru Ermias, Lee Stefi, Harris Rebecca, Yang Jianjun, Cho Soo Jung, Stout-Delgado Heather
Weill Cornell Medicine, Division of Pulmonary and Critical Care, New York, NY 10022, USA.
Vaccines (Basel). 2020 Jun 11;8(2):298. doi: 10.3390/vaccines8020298.
Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 10 PFU). Control and influenza-infected mice were instilled with PBS or (1 × 10 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with .
病毒印记引起的先天性和适应性免疫反应变化可对继发感染和疫苗反应产生重大的直接或间接影响。我们当前研究的目的是调查流感免疫印记在老年小鼠肺部感染期间对肺炎球菌疫苗效力的作用。成年老龄（18个月）小鼠接种肺炎球菌多价疫苗Pneumovax（5毫克/小鼠）。接种疫苗14天后，给小鼠滴注磷酸盐缓冲盐水（PBS）或甲型流感病毒A/PR8/34（3.5×10个噬斑形成单位）。在感染第7天，给对照小鼠和感染流感的小鼠滴注PBS或肺炎链球菌（1×10个菌落形成单位，美国典型培养物保藏中心6303），并评估肺部的抗菌免疫反应。我们的结果表明，作为对原发性流感感染的反应，细菌清除减少，促炎细胞因子如白细胞介素6（IL6）和白细胞介素1β（IL1β）的产生增加。接种Pneumovax疫苗通过调节核因子κB（NFҡB）表达降低促炎细胞因子的产生；然而，流感感染后这些反应显著减弱。综上所述，我们当前研究中的数据表明，流感免疫印记会降低肺炎球菌疫苗效力，从而可能导致老年人易发生继发感染。
