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.
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。