Cytotoxic T cell activity against the 22-kDa protein of human respiratory syncytial virus (RSV) is associated with a significant reduction in pulmonary RSV replication.

Recombinant vaccinia viruses expressing the RSV F glycoprotein (Vac-F), or a previously described chimeric protein consisting of the extracellular domains of the F and G glycoproteins (Vac-FG), or the 22-kDa membrane protein (Vac-22 kDa) were evaluated for their ability to protect BALB/c mice against infection by RSV subgroup A or subgroup B viruses and for their ability to induce a humoral immune response or a cytolytic T lymphocyte (CTL) response. Immunization with Vac-F or Vac-FG fully protected mice against challenge with RSV of subgroup A or B and induced high levels of both humoral and CTL-mediated immunity. Immunization with Vac-22 kDa partially to fully protected mice against challenge with RSV of subgroup A or B, depending on the immunization and challenge conditions, and induced a potent CTL response in the apparent absence of a significant humoral response. These vectors fortuitously allowed us to evaluate the contribution of a protein-specific memory CTL response to subgroup-specific and subgroup-cross-reactive reductions in pulmonary RSV replication independently from a humoral response. Our data suggest that 22-kDa-specific CTL contribute significantly to the reduction of RSV within the lung, but that complete protection also requires a humoral component.