Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No
vaccine is presently available to address this major unmet medical need. We generated a new genetic
vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified
Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1
proteins of RSV, for the induction of
neutralizing antibodies and broad cellular immunity. Because
RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent
infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower
respiratory tract infection in the absence of detectable
neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high
neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal
IgA against the F
protein. In conclusion, we have shown that our vectored
RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.