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

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 9

Serum and mucosal antibody responses in EBOV infection study 2.

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Serum and mucosal antibody responses in EBOV infection study 2. One dose...
One dose of aerosolized HPIV3/EboGP (n = 4; purple), 2 doses of aerosolized HPIV3/EboGP (n = 4; green), 2 doses of liquid HPIV3/EboGP (n = 2; red), and 2 doses of HPIV3 control (n = 2; black) were given. EBOV-specific IgG and IgA were detected in (A and B) serum and (D and E) concentrated BAL fluids by ELISA. EBOV-specific neutralizing antibodies were detected in (C) serum and (F) mucosa by plaque-reduction assays. TB, terminal bleed. Antibody titers are shown for individual animals in the vaccine groups, with the horizontal bar representing the group means. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, by 2-way ANOVA with Tukey’s post-hoc test. For clarity, comparisons made are shown only for the final time point.