Investigators in the Vanderbilt Vaccine Center are developing and testing new vaccines for respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) the most common causes of wheezing and pneumonia in children. We have developed several experimental vaccines that are in preclinical development stages, moving toward clinical trials.
Alphavirus-vectored RSV Vaccine
For this vaccine candidate, scientists in the Crowe laboratory collaborated with investigators at UNC-Chapel Hill to insert the RSV or HMPV gene encoding a surface protein of the virus into a form of another virus (called an alpha virus) that does not replicate. After intramuscular inoculation, the defective alphavirus enters cells and delivers the RSV or HMPV gene, which make the RSV or HMPV protein in the body. The protein immunizes the recipient because the body's immune systems react to the RSV or HMPV protein and generates antibodies and T cells that protect the recipient when later exposed. These candidate vaccines have been tested successfully in several small animal species and in monkeys. The vaccines are being prepared for clinical trials. These vaccines have been described in several publications to date:
- Mok H, Lee S, Utley TJ, Shepherd BE, Polosukhin VV, Collier ML, Davis NL, Johnston RE, Crowe JE Jr. Venezuelan equine encephalitis replicon particle vaccines encoding respiratory syncytial virus surface glycoproteins induce mucosal responses and protection in mice and cotton rats. Journal of Virology 2007; 81:13710-22. PMCID: 2168850.
- Mok H, Tollefson SJ, Podsiad AB, Shepherd BE, Polosukhin VV< Jonston RE, Williams JV, Crowe JE Jr. An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats. Journal of Virology 2008; 82:11410-8. PMCID: 2573258.
Computationally Designed RSV Vaccine
For the experiemental RSV vaccine, the Crowe laboratory has worked with investigators at the Scripps Research Institute and at Children's Hospital of Philadelphia to develop and test a new RSV vaccine. In this case, the structure of a protective RSV antibody with an RSV protein was already known in the literature. Scripps researched and computationally designed a protein that mimicked the surface of the RSV protein at the site of antibody binding. This synthetic protein was used as a vaccine, and indeed it induced high levels of protective antibodies in animal models. This vaccine candidate is being further developed.
Dr. Crowe presented data on this vaccine at the 8th Annual International Respiratory Virus Symposium (RSV 2012) meeting in Santa Fe, New Mexico.