Live attenuated influenza vaccine enhances colonization of Streptococcus pneumoniae and Staphylococcus aureus in mice.
Live attenuated influenza vaccine enhances colonization of Streptococcus pneumoniae and Staphylococcus aureus in mice.
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DOI：
10.1128/mbio.01040-13
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发表时间：
2014-02-18
期刊：
影响因子：
6.4
通讯作者：
Klugman KP
中科院分区：
文献类型：
--
作者：
Mina MJ;McCullers JA;Klugman KP
病毒（如流感病毒）和呼吸道细菌病原体之间在粘膜表面的群落相互作用是细菌性疾病发病机制的重要贡献者。尚未考虑的是这些相互作用对减毒活免疫的自然延伸，特别是减毒活流感疫苗（LAIV）。使用针对携带与人流感疫苗相同突变的甲型流感（H3N2）病毒的小鼠适应性LAIV，我们发现LAIV疫苗接种逆转了鼻咽部的正常细菌清除，并显著增加了小鼠上呼吸道内临床重要细菌病原体肺炎链球菌（血清型19 F和7 F）和金黄色葡萄球菌（菌株纽曼和赖特）的细菌携带密度。接种LAIV也导致细菌携带的平均持续时间增加2至5倍。此外，我们表明，在运输密度和持续时间的增加几乎是相同的，在所有方面的变化，细菌定植动力学感染野生型（WT）流感病毒。重要的是，LAIV与WT流感病毒不同，对下呼吸道内的严重细菌性疾病或死亡率没有影响。据我们所知，我们的研究结果是第一个证明用减毒活病毒疫苗接种可以直接调节重要和不相关的人类细菌病原体的定殖动力学，并且以与野生型病毒感染后观察到的高度相似的方式进行。感染流感病毒后，感染或最近恢复的个体变得对过量细菌感染，特别是肺炎链球菌和金黄色葡萄球菌短暂易感。事实上，在没有预先存在的合并症的情况下，细菌感染是流感流行期间严重疾病的主要原因。虽然这种协同作用是已知的，并进行了充分的研究，但尚未探索的是这些相互作用对减毒活流感疫苗（LAIV）的自然延伸。在这里，我们表明，在小鼠中，LAIV疫苗接种引发上呼吸道增加细菌生长和细菌携带的持久性，其方式几乎与野生型流感病毒感染后所见相同。重要的是，LAIV与野生型病毒不同，不会增加下呼吸道的严重细菌性疾病。这些发现可能对上呼吸道内的个体细菌性疾病过程以及LAIV疫苗接种人群中的细菌传播动力学产生影响
Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. Following infection with an influenza virus, infected or recently recovered individuals become transiently susceptible to excess bacterial infections, particularly Streptococcus pneumoniae and Staphylococcus aureus. Indeed, in the absence of preexisting comorbidities, bacterial infections are a leading cause of severe disease during influenza epidemics. While this synergy has been known and is well studied, what has not been explored is the natural extension of these interactions to live attenuated influenza vaccines (LAIVs). Here we show, in mice, that vaccination with LAIV primes the upper respiratory tract for increased bacterial growth and persistence of bacterial carriage, in a manner nearly identical to that seen following wild-type influenza virus infections. Importantly, LAIV, unlike wild-type virus, did not increase severe bacterial disease of the lower respiratory tract. These findings may have consequences for individual bacterial disease processes within the upper respiratory tract, as well as bacterial transmission dynamics within LAIV-vaccinated populations