Aerosolized Ebola vaccine protects primates
Ebola virus causes severe hemorrhagic fever and is readily transmitted through contact with or inhalation of aerosolized biological fluids from infected individuals. Vaccines against this deadly virus are currently in development. As Ebola outbreaks often occur in areas of Africa that lack infrastructure and trained medical personal, development of a needle-free vaccine would be advantageous. In this episode, Alexander Bukreyev and Michelle Meyer discuss their work, which demonstrates that an aerosolized formulation of an Ebola vaccine protects rhesus macaques from infection. The aerosolized version of the vaccine elicited an Ebola-specific response that was on par or better that an injected, liquid form of the same vaccine. Importantly, a single vaccination with the aerosolized formulation conferred 100% protection to macaques exposed to a lethal dose of Ebola virus. Together, these results support evaluation of the aerosolized vaccine formulation in clinical trials.
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Abstract
Direct delivery of aerosolized vaccines to the respiratory mucosa elicits both systemic and mucosal responses. This vaccine strategy has not been tested for Ebola virus (EBOV) or other hemorrhagic fever viruses. Here, we examined the immunogenicity and protective efficacy of an aerosolized human parainfluenza virus type 3–vectored vaccine that expresses the glycoprotein (GP) of EBOV (HPIV3/EboGP) delivered to the respiratory tract. Rhesus macaques were vaccinated with aerosolized HPIV3/EboGP, liquid HPIV3/EboGP, or an unrelated, intramuscular, Venezuelan equine encephalitis replicon vaccine expressing EBOV GP. Serum and mucosal samples from aerosolized HPIV3/EboGP recipients exhibited high EBOV-specific IgG, IgA, and neutralizing antibody titers, which exceeded or equaled titers observed in liquid recipients. The HPIV3/EboGP vaccine induced an EBOV-specific cellular response that was greatest in the lungs and yielded polyfunctional CD8+ T cells, including a subset that expressed CD103 (αE integrin), and CD4+ T helper cells that were predominately type 1. The magnitude of the CD4+ T cell response was greater in aerosol vaccinees. The HPIV3/EboGP vaccine produced a more robust cell-mediated and humoral immune response than the systemic replicon vaccine. Moreover, 1 aerosol HPIV3/EboGP dose conferred 100% protection to macaques exposed to EBOV. Aerosol vaccination represents a useful and feasible vaccination mode that can be implemented with ease in a filovirus disease outbreak situation.
Authors
Michelle Meyer, Tania Garron, Ndongala M. Lubaki, Chad E. Mire, Karla A. Fenton, Curtis Klages, Gene G. Olinger, Thomas W. Geisbert, Peter L. Collins, Alexander Bukreyev
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ISSN: 0021-9738 (print), 1558-8238 (online)