Pre-transplant vaccination against pulmonary viral infection

描述(由申请人提供)：造血细胞移植(HCT)后的感染并发症是一个重要的医疗保健问题。HCT患者患严重呼吸道感染的风险增加，其中呼吸道合胞病毒(RSV)感染是最常见的感染之一。在普通人群中，呼吸道合胞病毒感染很常见，几乎每个人都是在三岁之前感染的。然而，对RSV的保护性免疫是不完整的，因为在整个生命过程中感染是很常见的。在具有免疫能力的成年人中，这些症状通常与普通感冒(鼻病毒)相似。另一方面，在移植受者中，下呼吸道感染RSV是一个重要的死亡原因。在拟议的研究中，我们将测试一种在移植后早期控制呼吸道感染的新方法。几年来，我们一直在开发鼻用灭活病毒疫苗，以对抗呼吸道病毒，包括RSV。目前还没有获得许可的RSV疫苗，治疗方案也不太理想。造血细胞移植(HCT)患者是RSV疫苗接种的理想目标人群。首先，HCT患者在移植后相对较短的时间内感染呼吸道合胞病毒的风险最高。因此，一种成功的疫苗不一定需要提供长期保护。其次，即使对RSV的免疫力稍有改善，也可能对临床有益。第三，免疫经验丰富的成年人接种疫苗不太可能导致与1960年代S的福尔马林灭活呼吸道合胞病毒疫苗相关的疫苗增强型疾病。为此，我们发展了一种新的同种异体红细胞压积相关呼吸道合胞病毒感染模型。B6小鼠通常对RSV感染具有抵抗力，但在异基因造血细胞移植(Allo-HCT)后，它们明显更容易受到感染。我们将通过以下两个目标来探讨移植前接种RSV的潜在好处：目的1：确定移植前接种活疫苗和灭活疫苗对RSV易感性的免疫原性和有效性。目的2：共同探讨移植后对RSV的免疫机制，这些研究将使我们能够确定在造血细胞/骨髓移植之前接种疫苗是否可以预防移植后呼吸道感染。

DESCRIPTION (provided by applicant): Infectious complications following hematopoietic cell transplant (HCT) are a significant healthcare problem. HCT patients are at increased risk for developing severe respiratory infections, of which respiratory syncytial virus (RSV) infection is among the most common. In the general population, infection with RSV is common, with nearly everyone infected by three years of age. However, protective immunity to RSV is incomplete, in that infections throughout life are commonplace. In immunocompetent adults, these typically present with symptoms similar to the common cold (rhinovirus). In transplant recipients, on the other hand, lower respiratory tract infection with RSV is a significant cause of death. In the proposed studies, we will test a new method to manage respiratory infection in the early post-transplant period. For several years, we have been developing nasally administered, inactivated viral vaccines against respiratory viruses, including RSV. No licensed vaccine currently exists for RSV, and therapeutic options are less than optimal. Hematopoitic cell transplant (HCT) patients are an ideal patient population to serve as an initial target population for RSV vaccination. First, HCT patients are at highest risk for respiratory infection with RSV for a relatively short time period after transplant. Thus, a successful vaccine would not necessarily need to provide long-term protection. Second, even a small improvement in immunity to RSV is likely to be of clinical benefit. Third, vaccination of immunologically experienced adults is unlikely to lead to "vaccine- enhanced disease" associated with formalin-inactivated RSV vaccines in the 1960's. To this end, we have developed a novel model of allogeneic HCT- associated RSV infection. B6 mice, normally resistent to RSV infection are dramatically more susceptible following allogeneic hematopoietic cell transplant (Allo-HCT). We will investigate the potential benefit of pre-transplant vaccination against RSV via pursuing the following two Aims: Aim 1: Determine the immunogenicity and efficacy of live versus inactivated pre-transplant vaccination on RSV susceptibility Aim 2: Interrogate the mechanisms of post-transplant immunity to RSV Together, these studies will allow us determine whether vaccinating patients prior to hematopoietic cell/ bone marrow transplant can prevent respiratory infection in the post-transplant period.