Pre-transplant vaccination against pulmonary viral infection

Seattle Children'S Hospital, Seattle WA

Investigators

Abstract

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.