Format

Send to

Choose Destination
Mol Ther Methods Clin Dev. 2015 May 20;2:15018. doi: 10.1038/mtm.2015.18. eCollection 2015.

Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.

Author information

1
ReiThera Srl , Rome, Italy (former Okairos Srl).
2
Cellular Biology and Neurobiology Institute (IBCN) National Research Council of Italy , Rome, Italy.
3
San Raffaele Scientific Institute , Milano, Italy.
4
The Pirbright Institute , Surrey, UK.
5
ReiThera Srl , Rome, Italy (former Okairos Srl) ; Keires AG , Basel, Switzerland.
6
ReiThera Srl , Rome, Italy (former Okairos Srl) ; CEINGE , Naples, Italy ; Department of Molecular Medicine and Medical Biotechnology, University Federico II , Naples, Italy.

Abstract

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.

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center