Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity
Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity
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DOI：
10.1016/j.vaccine.2018.01.029
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发表时间：
2018-03-14
期刊：
影响因子：
5.5
通讯作者：
Ciaramella, Giuseppe
中科院分区：
文献类型：
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作者：
John, Shinu;Yuzhakov, Olga;Ciaramella, Giuseppe
由于目前还没有获得批准的巨细胞病毒（CMV）疫苗，因此在移植患者中有效预防先天性感染和减少巨细胞病毒疾病的巨细胞病毒疫苗仍然是一个高度优先考虑的问题。虽然保护的确切相关性尚不清楚，但中和抗体和抗原特异性T细胞与控制感染有关。我们证明，用脂质纳米颗粒（LNP）包封编码CMV糖蛋白gB和五聚体复合物（PC）的修饰mRNA，免疫小鼠和非人灵长类动物（NHPs），可产生有效和持久的中和抗体滴度。由于孕妇和移植受体的保护性相关因素可能不同，我们开发了一种额外的mRNA疫苗，表达免疫优势的CMV T细胞抗原pp65。pp65疫苗与PC和gB的结合在小鼠体内引起了强大的多抗原T细胞反应。我们的数据表明，mRNA/LNP是一个多功能平台，可以开发疫苗接种策略，预防CMV感染和随后的疾病在不同的目标人群。(C) 2018作者。Elsevier Ltd.出版。
A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers. Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65. Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations. (C) 2018 The Author(s). Published by Elsevier Ltd.