A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.
A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.
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DOI：
10.1021/mp500646d
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发表时间：
2015-08-03
影响因子：
4.9
通讯作者：
Croyle MA
中科院分区：
文献类型：
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作者：
Choi JH;Jonsson-Schmunk K;Qiu X;Shedlock DJ;Strong J;Xu JX;Michie KL;Audet J;Fernando L;Myers MJ;Weiner D;Bajrovic I;Tran LQ;Wong G;Bello A;Kobinger GP;Schafer SC;Croyle MA
随着西非埃博拉疫情的持续，美国和其他国家出现病例，迫切需要长效疫苗来保护全球健康。在这里，我们评估了两个阶段的非人灵长类动物的呼吸道和舌下（SL）腺病毒为基础的疫苗的长期疗效。在第一项研究中，单次呼吸道剂量为1.4 × 109个感染性病毒颗粒（ivp）/kg的Ad-CAGoptZGP诱导了强烈的埃博拉糖蛋白（GP）特异性CD 8+和CD 4 + T细胞应答以及全身和粘膜区室中的埃博拉GP特异性抗体，并在免疫后62天对攻击具有部分（67%）保护作用。通过SL途径给予的相同剂量诱导的埃博拉GP特异性CD 8 + T细胞应答与肌内（IM）注射相似，然而，埃博拉GP特异性抗体应答较低。所有灵长类动物都死于感染。然后给三只灵长类动物注射了一种疫苗，这种疫苗可以提高啮齿动物对埃博拉病毒的免疫反应。用2.0 × 1010 ivp/kg疫苗通过SL途径免疫3只灵长类动物。在呼吸道免疫后150天收集的样品中存在多功能埃博拉GP特异性CD 4+和CD 8 + T细胞和显著抗埃博拉GP抗体的不同群体。配制的疫苗在免疫后21周对攻击具有完全保护性。虽然SL免疫后产生了不同的埃博拉GP特异性CD 4 + T细胞群体，但抗体不能中和，疫苗没有保护性。据我们所知，这是首次在灵长类动物中证明单剂量呼吸道腺病毒埃博拉疫苗的持久保护作用。
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 × 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 × 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.