Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
Med. 2021 Mar 12;2(3):243-262.e8. doi: 10.1016/j.medj.2020.12.006. Epub 2020 Dec 16.
The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults.
Here, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice.
A single vaccination generates spike-specific Th1 cells, Th1-like Foxp3 regulatory T cells, polyfunctional spike-specific CD8 T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice.
This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons.
This study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK.
SARS-CoV-2 的传播引发了全球大流行，几乎影响了人类生活的方方面面。开发有效的 COVID-19 疫苗可以限制感染引起的发病率和死亡率，并可能使社会隔离措施得以放松。年龄是感染 SARS-CoV-2 后健康状况不佳的最重要危险因素之一；因此，理想情况下，任何新的疫苗候选物都能在老年人中引发强大的免疫反应。
在这里，我们使用深度免疫表型分析来描述在肌肉内给予腺病毒载体 ChAdOx1 nCoV-19（AZD-1222）COVID-19 疫苗候选物后，在小鼠中诱导的先天和适应性免疫反应。
单次接种可产生刺突特异性 Th1 细胞、Th1 样 Foxp3 调节性 T 细胞、多效性刺突特异性 CD8 T 细胞和颗粒酶-B 产生的 CD8 效应物。刺突特异性 IgG 和 IgM 由早期滤泡外抗体反应和滤泡辅助性 T 细胞支持的生发中心反应产生，这与产生病毒中和抗体有关。单次给予这种疫苗可在老年小鼠中产生类似的免疫反应，但程度低于年轻小鼠。我们报告说，第二剂可增强老年小鼠对这种疫苗的免疫反应。
这项研究表明，ChAdOx1 nCoV-19 在成年和老年小鼠中诱导细胞和体液免疫，并表明初次免疫-加强免疫策略是增强老年人免疫原性的合理方法。
这项研究得到了 BBSRC、李斯特预防医学研究所、EPSRC VaxHub 和 Innovate UK 的支持。
