A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection

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• 作者：Jin Huk Choi ; Kristina Jonsson-Schmunk ; Xiangguo Qiu ; Devon J. Shedlock ; Jim Strong ; Jason X. Xu ; Kelly L. Michie ; Jonathan Audet ; Lisa Fernando ; Mark J. Myers ; David Weiner ; Irnela Bajrovic ; Lilian Q. Tran ; Gary Wong ; Alexander Bello ; Gary P. Kobinger ; Stephen C. Schafer ; Maria A. Croyle
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：August 3, 2015
• 年：2015
• 卷：12
• 期：8
• 页码：2712-2731
• 全文大小：1225K
• ISSN：1543-8392

文摘

As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4 脳 10⁹ infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8⁺ and CD4⁺ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8⁺ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0 脳 10¹⁰ ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4⁺ and CD8⁺ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4⁺ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates.