Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses
Michelle Meyer, … , Peter L. Collins, Alexander Bukreyev
Michelle Meyer, … , Peter L. Collins, Alexander Bukreyev
Published August 3, 2015; First published July 13, 2015
Citation Information: J Clin Invest. 2015;125(8):3241-3255. https://doi.org/10.1172/JCI81532.
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Categories: Research Article Vaccines

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

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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Figure 1

Schedules of vaccinations, biosamplings, and EBOV exposure.

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Schedules of vaccinations, biosamplings, and EBOV exposure. (A) Study 1:...
(A) Study 1: NHP immune response to vaccination. Groups of rhesus macaques were vaccinated with HPIV3/EboGP as an aerosol (n = 4; green) or a liquid via the i.n./i.t. (n = 4; red) route, the empty HPIV3 vector control (n = 2; black), or the VRP vaccine by the i.m. route (n = 4; blue). Twenty-eight days after the first dose, all NHPs received a second dose of their respective vaccine. On day 56, NHPs were euthanized and mononuclear cells were extracted. (B) Study 2: testing of protective efficacy. Groups of rhesus macaques were vaccinated with 1 (n = 4; purple) or 2 doses (n = 4; green) of aerosolized HPIV3/EboGP, 2 doses of liquid HPIV3/EboGP (n = 2; red), or HPIV3 control (n = 2; black). Fifty-five days after vaccination, NHPs were infected with EBOV. At the end of the study, surviving animals were euthanized and terminal bleed samples were collected. Over the course of the 2 studies, serum and BAL samples were collected on indicated days.