Siggins Matthew K, Gill Simren K, Langford Paul R, Li Yanwen, Ladhani Shamez N, Tregoning John S
Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, UK.
Section of Paediatrics, Imperial College London, London W2 1PG, UK.
Vaccine. 2015 Sep 11;33(38):4954-61. doi: 10.1016/j.vaccine.2015.07.034. Epub 2015 Jul 26.
A recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD-CV; Synflorix, GSK) uses Protein D from Haemophilus influenzae as a carrier protein. PHiD-CV therefore has the potential to provide additional protection against nontypeable H. influenzae (NTHi). NTHi frequently causes respiratory tract infections and is associated with significant morbidity and mortality worldwide and there is currently no vaccine.
We developed mouse models of NTHi infection and influenza/NTHi superinfection. Mice were immunized with PHiD-CV, heat-killed NTHi, or a 13-valent pneumococcal conjugate vaccine that did not contain Protein D (PCV13; Prevenar, Pfizer) and then infected intranasally with NTHi.
Infection with NTHi resulted in weight loss, inflammation and airway neutrophilia. In a superinfection model, prior infection with pandemic H1N1 influenza virus (strain A/England/195/2009) augmented NTHi infection severity, even with a lower bacterial challenge dose. Immunization with PHiD-CV produced high levels of antibodies that were specific against Protein D, but not heat-killed NTHi. Immunization with PHiD-CV led to a slight reduction in bacterial load, but no change in disease outcome.
PHiD-CV induced high levels of Protein D-specific antibodies, but did not augment pulmonary clearance of NTHi. We found no evidence to suggest that PHiD-CV will offer added benefit by preventing NTHi lung infection.
一种最近获批的10价肺炎球菌结合疫苗(PHiD-CV;Synflorix,葛兰素史克公司)使用来自流感嗜血杆菌的D蛋白作为载体蛋白。因此,PHiD-CV有可能提供针对不可分型流感嗜血杆菌(NTHi)的额外保护。NTHi经常引起呼吸道感染,在全球范围内与显著的发病率和死亡率相关,并且目前尚无疫苗。
我们建立了NTHi感染和流感/NTHi重叠感染的小鼠模型。用PHiD-CV、热灭活的NTHi或不含D蛋白的13价肺炎球菌结合疫苗(PCV13;沛儿,辉瑞公司)对小鼠进行免疫,然后经鼻内感染NTHi。
感染NTHi导致体重减轻、炎症和气道中性粒细胞增多。在重叠感染模型中,即使细菌攻击剂量较低,先前感染大流行性H1N1流感病毒(A/England/195/2009株)也会增加NTHi感染的严重程度。用PHiD-CV免疫产生了高水平的针对D蛋白的特异性抗体,但对热灭活的NTHi则没有。用PHiD-CV免疫导致细菌载量略有降低,但疾病结局没有变化。
PHiD-CV诱导产生高水平的D蛋白特异性抗体,但并未增强肺部对NTHi的清除。我们没有发现证据表明PHiD-CV能通过预防NTHi肺部感染带来额外益处。