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Developmental Research Project DP007

Collaborating Institution: University of Texas Medical Branch, Galveston, TX

Principal Investigator: Alexander Bukreyev, PhD

Title of the Project: Aerosol Vaccination Against Ebola Virus

Expected Product: A mucosal vaccine against Ebola virus, tested in nonhuman primates.

Description: Mucosal respiratory tract vaccination against Ebola virus with a previously developed vaccine based on a human parainfluenza virus type 3 vector (HPIV3/EboGP) was completely protective against a highly lethal challenge against Ebola virus in nonhuman primates (NHP). The vaccine has important advantages including the induction of a strong mucosal immune response in the respiratory tract and the needle-free delivery. The most practical and the most effective way to deliver mucosal respiratory tract vaccines is by disposable nebulizers in an aerosolized form. However, this delivery method has never been tested for vaccines against Ebola virus or any other viral hemorrhagic fever. Moreover, induction of the virus-specific mucosal and antibody immune responses to mucosal respiratory tract vaccinations has never been fully characterized in humans or NHP, since all published studies included analysis of the cell-mediated responses in the peripheral blood only. However, it has been shown that only a small fraction of T lymphocytes specific for common respiratory viruses is located in the peripheral blood, while the majority of the cells do not migrate from the lung tissue, and the virus-specific T lymphocytes in lungs are phenotypically different and more activated as compared to those in the peripheral blood. It has also been shown that both the antibody and the cell-mediated responses are important for protection against Ebola virus. Therefore, the specific aims of the proposed study are the following. 1. Characterize the mucosal EBOV-specific T lymphocyte and antibody responses induced in lungs of NHP vaccinated by aerosolized HPIV3-vectored vaccine containing EBOV GP protein (HPIV3/EboGP). The study will include a comparison of respiratory tract responses to the systemic responses in the NHP vaccinated by aerosolized HPIV3/EboGP or an unrelated vaccine delivered by injection. 2. Determine whether vaccination with aerosolized HPIV3/EboGP delivered by the respiratory tract is protective against a lethal dose of EBOV in NHP.