Description): Respiratory Syncytial Virus(RSV) is the most common viral cause of lower respiratory tract disease in infants and young children throughout the world. The virus is unusual in its propensity to cause a peak incidence of severe disease resulting in hospitalization in the first two months of life. A major obstacle to successful immunization of neonates against disease caused by RSV is the fact that neonates make very poor antibody responses to primary infection at this young age. It is likely that this poor response results from immaturity in neonatal B and T lymphocytes. The central hypothesis of this project is that the B-cell repertoire expressed in the first weeks of life in humans does not specify RSV antibodies that possess the structural determinants required for effective virus neutralization. To test this hypothesis the investigators will isolate and characterize large panels of human RSV monoclonal antibodies from serial blood samples collected from neonates undergoing primary RSV infection, beginning with cord blood and including multiple samples in the first months of life. They will clone and sequence antibody genes from the B-cell clones and hybridomas obtained, then analyze the sequences for antibody gene family and segment usage, mutations and insertions. The RSV specific B-cell repertoire from neonates will be compared with that of the infants mothers. Each antibody will be fully characterized as to antiviral activity and specificity, thus allowing them to determine the genetic origins of RSV neutralization in humans. The data from this work will direct decisions about the best vaccine strategy to use against RSV in neonates, and will delineate basic mechanisms of the ontogeny of B-cell repertoire diversity in humans.
| Crowe Jr, J E (1999) Host responses to respiratory virus infection and immunization. Curr Top Microbiol Immunol 236:191-214 |
