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SARS-CoV-2 疫苗可在幼年恒河猴中引发持久的免疫应答。

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques.

机构信息

Duke University Medical Center, Duke Human Vaccine Institute, Durham, NC, USA.

Department of Microbiology and Immunology, Center for AIDS Research, and Children's Research Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Sci Immunol. 2021 Jun 15;6(60). doi: 10.1126/sciimmunol.abj3684.

Abstract

The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.

摘要

将婴儿纳入 SARS-CoV-2 疫苗接种计划对于预防儿科 SARS-CoV-2 感染的严重并发症以及限制传播非常重要,并且可以通过全球儿科疫苗接种计划来实施。然而,免疫功能的年龄依赖性差异需要在儿科人群中仔细评估新型疫苗。为此,我们评估了两种 SARS-CoV-2 疫苗的安全性和免疫原性。两组 8 只婴儿恒河猴(RMs)分别在 0 周和 4 周时通过肌肉内注射用 mRNA 包裹在脂质纳米颗粒(mRNA-LNP)编码的稳定预融合 SARS-CoV-2 S-2P 刺突(S)蛋白或与 3M-052 混合的纯化 S 蛋白进行免疫,3M-052 是一种在角鲨烯乳液中的合成 TLR7/8 激动剂(Protein+3M-052-SE)。两种疫苗均未引起不良反应。两种疫苗均诱导产生针对 RBD、N 端结构域、S1 和 S2、ACE2 阻断活性的高滴度 IgG 结合物以及高中和抗体滴度,所有这些均在第 6 周达到峰值。在第 4 周时检测到 S 特异性记忆 B 细胞,S 特异性 T 细胞反应主要由 IL-17、IFN-γ 或 TNF-α的产生主导。抗体和细胞反应在第 22 周时保持稳定。mRNA-LNP 疫苗的免疫反应与成人中 Moderna mRNA-1273 疫苗引起的免疫反应相似。S-2P mRNA-LNP 和 Protein-3M-052-SE 疫苗在婴儿 RMs 中耐受性良好且具有高度免疫原性,为儿科 SARS-CoV-2 疫苗提供了概念验证,该疫苗具有持久免疫的潜力,可能减少 SARS-CoV-2 的传播并减轻 COVID-19 造成的持续健康和社会经济影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ee/8774290/dcf6e25c71cc/nihms-1770510-f0001.jpg

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