Respiratory Syncytial Virus; Anti-viral immunity in humans and macaques.

The results presented in this thesis show that hRSV infection in humans results in a multifaceted immune response, which cannot be described as purely Th1- or Th2-like. However, the observed higher level of IL-13 producing hRSV-specific T cells in infants hospitalized with severe hRSV bronchiolitis could provide a clue for an immunopathological mechanism of natural hRSV-mediated severe disease. Another hRSV-specific immunological factor potentially involved in the pathogenesis of severe hRSV disease could be the frequency and/or phenotype like those of HLADP4-restricted T cell responses directed to the conserved region of the RSV G protein. The BBG2Na- and rMVA-F/G-based vaccination strategies evaluated in infant macaques resulted in low VN and cellular immune responses and no detectable protection. A combination of both approaches in a prime-boost regime could possibly increase vaccine immunogenicity, but in this case the immunopathological safety would again have to be evaluated in different animal models.