Vaccination with the RSV fusion protein formulated with a combination adjuvant induces long-lasting protective immunity

Respiratory syncytial virus (RSV) is one of the primary causative agents of upper and lower respiratory tract infections in young children, in particular infants. Recently, we reported the protective efficacy of a RSV vaccine formulation consisting of a truncated version of the fusion (F) protein formulated with a Toll-like receptor (TLR) agonist and an immunostimulatory peptide in a carrier system (Delta F/TriAdj). To evaluate the duration of immunity induced by this vaccine candidate, we carried out long-term trials. The Delta F was formulated with triple adjuvant (TriAdj) containing either polyinosinic : polycytidylic acid (polyl:C) or cytosine-phosphate-guanosine oligodeoxpucleotides (CpG ODNs) and administered intranasally to mice. One year after the second vaccination all mice were challenged with RSV. Both Delta F/TriAdj formulations mediated the induction of high levels of IgG1, IgG2a and virus-neutralizing antibodies, and IgA in the lungs. Based on the numbers of IFN-gamma- and IL-5-secreting cells in the spleen, the immune response was slightly T-helper cell type 1 (Th1)-biased. This was confirmed by the presence of F85-93-specific CD8(+) effector T cells in the lungs of both Delta F/TriAdj(polyl:C)- and Delta F/TriAdj(CpG)-immunized mice. Both Delta F/TriAdj formulations induced RSV-specific CD8(+) T cells. However, Delta F/TriAdj(polyl:C) generated significantly higher IgG affinity maturation and higher numbers of RSV-specific CD8(+) effector memory T cells in lungs and CD8(+) central memory T cells in spleen and lymph nodes than Delta F/TriAdj(CpG). After RSV challenge, no virus replication and no evidence of vaccine-induced pathology were detected in mice immunized with either of the Delta F/TriAdj formulations, demonstrating that the duration of immunity induced with these vaccines is at least one year.