PROTECTION AGAINST RESPIRATORY SYNCYTIAL VIRUS-INFECTION BY DNA IMMUNIZATION

Respiratory syncytial virus (RSV) remains a major cause of morbidity a nd mortality in infants and dir elderly and is a continuing challenge for vaccine development. A murine T helper cell (Th) type 2 response a ssociates with enhanced lung pathology, which has been observed in pas t infant trials using formalin-inactivated RSV vaccine. In this study, we have engineered an optimized plasmid DNA vector expressing the RSV fusion (F) protein (DNA-F). DNA-F was as effective as Live RSV in mic e at inducing neutralizing antibody and cytotoxic T lymphocyte respons es, protection against infection, and high mRNA expression of lung int erferon gamma after viral challenge. Furthermore, a DNA-F boost could switch a preestablished anti-RSV Th2 response towards a Th1 response. Critical elements for the optimization of the plasmid constructs inclu ded expression of a secretory form of the F protein and the presence o f the rabbit P-globin intron II sequence upstream of the F-encoding se quence. In addition, anti-F systemic immune response profile could be modulated by the route of DNA-F delivery: intramuscular immunization r esulted in balanced responses, whereas intradermal immunization result ed in a Th2 type of response. Thus, DNA-F immunization may provide a n ovel and promising RSV vaccination strategy.