Abstract：
BACKGROUND: Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM.
METHODS: Safety and efficacy of intranasal H haemolyticus at 5 × 107 colony-forming units (CFU) was tested in female BALB/cARC mice using an influenza model and influenza-driven nontypeable Haemophilus influenzae (NTHi) OM model. Weight, symptoms, viral/bacterial levels, and immune responses were measured.
RESULTS: Intranasal delivery of H haemolyticus was safe and reduced severity of influenza, with quicker recovery, reduced inflammation, and lower lung influenza virus titers (up to 8-fold decrease vs placebo; P ≤ .01). Haemophilus haemolyticus reduced NTHi colonization density (day 5 median NTHi CFU/mL = 1.79 × 103 in treatment group vs 4.04 × 104 in placebo, P = .041; day 7 median NTHi CFU/mL = 28.18 vs 1.03 × 104; P = .028) and prevented OM (17% OM in treatment group, 83% in placebo group; P = .015).
CONCLUSIONS: Haemophilus haemolyticus has potential as a live biotherapeutic for prevention or early treatment of influenza and influenza-driven NTHi OM. Additional studies will deem whether these findings translate to humans and other respiratory infections.
METHODS: Safety and efficacy of intranasal H haemolyticus at 5 × 107 colony-forming units (CFU) was tested in female BALB/cARC mice using an influenza model and influenza-driven nontypeable Haemophilus influenzae (NTHi) OM model. Weight, symptoms, viral/bacterial levels, and immune responses were measured.
RESULTS: Intranasal delivery of H haemolyticus was safe and reduced severity of influenza, with quicker recovery, reduced inflammation, and lower lung influenza virus titers (up to 8-fold decrease vs placebo; P ≤ .01). Haemophilus haemolyticus reduced NTHi colonization density (day 5 median NTHi CFU/mL = 1.79 × 103 in treatment group vs 4.04 × 104 in placebo, P = .041; day 7 median NTHi CFU/mL = 28.18 vs 1.03 × 104; P = .028) and prevented OM (17% OM in treatment group, 83% in placebo group; P = .015).
CONCLUSIONS: Haemophilus haemolyticus has potential as a live biotherapeutic for prevention or early treatment of influenza and influenza-driven NTHi OM. Additional studies will deem whether these findings translate to humans and other respiratory infections.
摘要：
背景：尽管接种了疫苗，流感和中耳炎（OM）仍然是疾病的主要原因。我们先前发现，人类呼吸道共生溶血嗜血杆菌可在体外预防细菌感染，而相关的鼠共生Muribactermuris可延迟小鼠的OM发育。Mmuris预处理降低肺流感滴度和炎症的观察表明，这些细菌可用于预防流感/OM。
方法：使用流感模型和流感驱动的不可分型的流感嗜血杆菌（NTHi）OM模型，在雌性BALB/cARC小鼠中测试了5×107个集落形成单位（CFU）的鼻内溶血H的安全性和功效。重量,症状,病毒/细菌水平，并测量了免疫反应。
结果：溶血H鼻内给药是安全的，并且降低了流感的严重程度，随着更快的恢复，减少炎症，和较低的肺流感病毒滴度（与安慰剂相比下降了8倍；P≤0.01）。溶血嗜血杆菌降低NTHi定植密度(第5天NTHiCFU/mL中位数治疗组=1.79×103vs安慰剂组4.04×104,P=.041；第7天NTHiCFU/mL中位数=28.18vs1.03×104；P=.028）和预防OM（治疗组中为17％OM，安慰剂组为83%；P=0.015）。
结论：溶血嗜血杆菌具有作为预防或早期治疗流感和流感驱动的NTHiOM的活性生物治疗剂的潜力。其他研究将考虑这些发现是否会转化为人类和其他呼吸道感染。
方法：使用流感模型和流感驱动的不可分型的流感嗜血杆菌（NTHi）OM模型，在雌性BALB/cARC小鼠中测试了5×107个集落形成单位（CFU）的鼻内溶血H的安全性和功效。重量,症状,病毒/细菌水平，并测量了免疫反应。
结果：溶血H鼻内给药是安全的，并且降低了流感的严重程度，随着更快的恢复，减少炎症，和较低的肺流感病毒滴度（与安慰剂相比下降了8倍；P≤0.01）。溶血嗜血杆菌降低NTHi定植密度(第5天NTHiCFU/mL中位数治疗组=1.79×103vs安慰剂组4.04×104,P=.041；第7天NTHiCFU/mL中位数=28.18vs1.03×104；P=.028）和预防OM（治疗组中为17％OM，安慰剂组为83%；P=0.015）。
结论：溶血嗜血杆菌具有作为预防或早期治疗流感和流感驱动的NTHiOM的活性生物治疗剂的潜力。其他研究将考虑这些发现是否会转化为人类和其他呼吸道感染。
