Immunogenicity assays are detailed below and sample processing and analyses of all immunology data was performed observer blinded by use of a randomly generated laboratory identifier

Immunogenicity assays are detailed below and sample processing and analyses of all immunology data was performed observer blinded by use of a randomly generated laboratory identifier. T-cell responses were increased after IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. IFN secretion after boost was from both CD4+ and CD8+ T-cells, without detectable Th2 cytokines that have been previously associated with immune pathogenesis following exposure to RSV after formalin inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease. Keywords: Respiratory syncytial virus, vaccine, phase I, adenovirus, MVA INTRODUCTION Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection throughout life with young infants and the elderly especially susceptible to developing severe disease. There is only supportive care for cases of infection. Despite decades of research effort there remains no licensed vaccine for the prevention of severe disease, and the use of palivizumab monoclonal antibody prophylaxis is limited to high-risk infants only. The peak incidence of disease requiring hospitalisation is Sulfabromomethazine in the first few months of life (1). Infants with bronchiolitis account for up to 18% of winter paediatric admissions (2) and infection by RSV is responsible for almost 80% of cases (3). Two thirds of infants are infected by RSV in the first year of life (1) and 2-3% of primary infections require admission to hospital (4, 5). Approximately 6% of these admissions will require management on dedicated paediatric intensive care units (6). Worldwide, RSV disease in children under the age of 5 years account for an estimated 33.8 million lower respiratory tract infections, 3.4 million hospitalisations and up to 200,000 deaths annually (8). RSV-associated deaths are almost exclusive to resource poor areas of the world where RSV is second only to malaria in all-cause infant mortality between 1 and 12 months of age (7, 8). Cumulative RSV exposure produces an immune response capable of protection against severe lower respiratory tract disease but not protection from infection. 50% of infants suffer at least one RSV re-infection by their second birthday (1) and there is increasing evidence for causality between RSV infection in infancy and subsequent Sulfabromomethazine wheezing and possibly asthma in later life (9, 10). Healthy adults can expect a 7-9% annual risk of infection with mild symptomatic disease (11, 12) and severe immune suppression can re-establish Rabbit Polyclonal to KLF a risk of developing severe disease (13). Later in life, senescence of the immune system and comorbid conditions place the elderly at risk of developing severe RSV disease, and estimates of hospital burden and mortality from RSV in the elderly vary but may be comparable to seasonal Sulfabromomethazine influenza (14-16). The high rate of emergency admissions, lack of universal and cost-effective preventative measures and the magnitude of seasonal disease incidence maintain RSV as a major priority for vaccine development (17). Concerns over safety and an incomplete understanding of the immune correlates of protection have hampered efforts to develop such a vaccine. The formalin-inactivated RSV vaccine candidate (FI-RSV), tested nearly 50 years ago, led to enhanced respiratory disease (ERD) upon RSV exposure. ERD, which had a propensity to manifest in the youngest infants, caused 80% to become hospitalised over the subsequent RSV transmission season (compared to 5% in controls) and two fatalities in FI-RSV recipients (18-21). Animal challenge experiments and post-mortem lung histology from the infant fatalities implicated ERD as a vaccine-primed Th2-associated immunopathology following exposure to natural RSV infection, and has cast a long shadow over subsequent vaccine design and development. Subunit vaccine formulations have therefore remained in development for seropositive target populations and as maternal vaccines. Intra-nasal live attenuated RSV vaccine candidates, whose development.