Novel vaccines for otitis media

描述（由申请人提供）：本提案符合临床研究中两个主要挑战领域的要求，即“预防中耳炎”（04-DC 101）和“开发新方法并解决粘膜免疫学中的关键问题”（04-AI-101）。 肺炎链球菌引起的中耳炎是儿童的一个重大医疗负担。虽然肺炎球菌多价结合疫苗Prevnar的出现总体上降低了肺炎球菌疾病的负担，但次优的粘膜免疫应答已证明在引发有效保护方面存在问题。即使接种了疫苗，急性中耳炎也是儿科医生就诊的主要原因，并且是为幼儿处方的大多数抗生素的原因。这强调了开发新的疫苗接种策略和更好地了解宿主粘膜免疫的重要性。为此，鼻内疫苗接种由于在诱导强粘膜免疫应答方面的潜在有效性而作为替代策略最近获得了相当大的关注。我们建议使用新描述的，强大的动物模型来评估两种新型肺炎球菌减毒活疫苗对中耳炎的免疫应答和保护效果。这些数据有望扩大我们对中耳炎粘膜免疫的认识，并为临床提供有用的临床前数据，以推进新型疫苗的临床应用。 公共卫生相关性：肺炎链球菌引起的中耳炎给儿童带来了巨大的医疗负担。虽然肺炎球菌多价结合疫苗Prevnar的出现总体上降低了肺炎球菌疾病的负担，但次优的粘膜免疫应答已证明在引发有效保护方面存在问题。即使接种了疫苗，急性中耳炎也是儿科医生就诊的主要原因，并且是为幼儿处方的大多数抗生素的原因。这突出表明 开发新的疫苗接种策略和更好地了解宿主粘膜免疫的重要性。为此，鼻内疫苗接种由于在诱导强粘膜免疫应答方面的潜在有效性而作为替代策略最近获得了相当大的关注。我们建议使用新描述的， 强大的动物模型。这些数据有望扩大我们对中耳炎粘膜免疫的认识，并为临床提供有用的临床前数据，以推进新型疫苗的临床应用。

DESCRIPTION (provided by applicant): This proposal meets the requirements of two major Challenge Areas within Clinical Research, "Prevention of otitis media" (04-DC101), and "Develop novel methods and address key questions in mucosal immunology" (04-AI-101). Otitis media caused by Streptococcus pneumoniae represents a significant medical burden in children. While the advent of the pneumococcal polyvalent conjugate vaccine Prevnar has decreased the burden of pneumococcal disease overall, the suboptimal mucosal immune response has proved problematic in eliciting effective protection. Even with vaccination, acute otitis media is the leading cause of pediatric physician visits and is responsible for a majority of the antibiotics prescribed to young children. This underscores the importance of development of new vaccination strategies and a greater understanding of host mucosal immunity. To this end, intranasal vaccination has recently gained considerable attention as an alternative strategy due to potential effectiveness at inducing a robust mucosal immune response. We propose to evaluate the immune responses and protective efficacy of two novel live, attenuated pneumococcal vaccines against otitis media using newly described, robust animal models. These data are expected to expand our knowledge of mucosal immunity to otitis media and provide pre-clinical data useful for advancing novel vaccines to the clinic. PUBLIC HEALTH RELEVANCE: Otitis media caused by Streptococcus pneumoniae represents a significant medical burden in children. While the advent of the pneumococcal polyvalent conjugate vaccine Prevnar has decreased the burden of pneumococcal disease overall, the suboptimal mucosal immune response has proved problematic in eliciting effective protection. Even with vaccination, acute otitis media is the leading cause of pediatric physician visits and is responsible for a majority of the antibiotics prescribed to young children. This underscores the importance of development of new vaccination strategies and a greater understanding of host mucosal immunity. To this end, intranasal vaccination has recently gained considerable attention as an alternative strategy due to potential effectiveness at inducing a robust mucosal immune response. We propose to evaluate the immune responses and protective efficacy of two novel live, attenuated pneumococcal vaccines against otitis media using newly described, robust animal models. These data are expected to expand our knowledge of mucosal immunity to otitis media and provide pre-clinical data useful for advancing novel vaccines to the clinic.