Intranasal coinfection model allows for assessment of protein vaccines against nontypeable Haemophilus influenzae in mice
Intranasal coinfection model allows for assessment of protein vaccines against nontypeable Haemophilus influenzae in mice
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DOI：
10.1099/jmm.0.000827
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发表时间：
2018-10-01
影响因子：
3
通讯作者：
Pichichero, Michael E.
中科院分区：
文献类型：
--
作者：
Michel, Lea Vacca;Kaur, Ravinder;Pichichero, Michael E.
目的.无法分型的流感嗜血杆菌（NTHi）是人鼻咽部的寄生虫，是肺炎、脑膜炎、鼻窦炎、慢性阻塞性肺病急性加重和急性中耳炎（AOM）的原因。AOM是美国最常见的抗生素处方疾病。随着新的耐药细菌菌株的出现，寻找有效且覆盖范围广的疫苗来保护免受AOM病原体的侵害已成为当务之急。小鼠模型是一种具有成本效益和有效的方法，以帮助确定疫苗的效力。在这里，我们描述了在C57 BL/6 J小鼠中的NTHi AOM模型，该模型也利用小鼠适应的H1N1流感病毒来模拟人类共感染。我们使用含有蛋白D的蛋白疫苗制剂测试了我们的合并感染模型，蛋白D是一种经过充分研究的NTHi疫苗候选物，可以在10价肺炎链球菌结合疫苗中找到。我们通过比较蛋白D接种小鼠和对照小鼠鼻和耳中的细菌载量来验证我们的小鼠模型的有用性。虽然鼻内细菌载量没有可测量的差异，但我们确实检测到接种小鼠和对照小鼠之间耳洗液和耳泡的细菌载量存在显著差异。本研究的结果表明，我们的NTHi AOM共感染模型可用于评估蛋白疫苗。
Purpose. Nontypeable Haemophilus influenzae (NTHi) is a commensal in the human nasopharynx and the cause of pneumonia, meningitis, sinusitis, acute exacerbations of chronic obstructive pulmonary disease and acute otitis media (AOM). AOM is the most common ailment for which antibiotics are prescribed in the United States. With the emergence of new strains of antibiotic-resistant bacteria, finding an effective and broad coverage vaccine to protect against AOM-causing pathogens has become a priority. Mouse models are a cost-effective and efficient way to help determine vaccine efficacy. Here, we describe an NTHi AOM model in C57BL/6J mice, which also utilizes a mouse-adapted H1N1 influenza virus to mimic human coinfection.Methodology. We tested our coinfection model using a protein vaccine formulation containing protein D, a well-studied NTHi vaccine candidate that can be found in the 10-valent Streptococcus pneumoniae conjugate vaccine. We verified the usefulness of our mouse model by comparing bacterial loads in the nose and ear between protein D-vaccinated and control mice.Results. While there was no measurable difference in nasal bacterial loads, we did detect significant differences in the bacterial loads of ear washes and ear bullae between vaccinated and control mice.Conclusion. The results from this study suggest that our NTHi AOM coinfection model is useful for assessing protein vaccines.