Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosa! surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (Delta F) protein formulated with polyl : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8(+) T-cells in the lung, when delivered intranasally. Furthermore, this Delta F protein formulation promoted the production of CD8(+) central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of Delta F protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The Delta F protein formulation was confirmed to be highly efficacious and safe in cotton rats.