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.
Nicholas
J A
JA
Department of Infectious Diseases, Upjohn Laboratories, Kalamazoo, Michigan 49007.
Rubino
K L
KL
Levely
M E
ME
Meyer
A L
AL
Collins
P L
PL
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006023:Glycoproteins / Q000276:immunology; D007111:Immunity, Cellular; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014760:Viral Fusion Proteins / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D008565:Membrane Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins