异源接种自扩增 RNA 和 mRNA COVID-19 疫苗后增强免疫应答。

Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.

机构信息

Department of Infectious Disease, Imperial College London, United Kingdom.

Imperial College Healthcare NHS Trust, London, United Kingdom.

出版信息

PLoS Pathog. 2022 Oct 4;18(10):e1010885. doi: 10.1371/journal.ppat.1010885. eCollection 2022 Oct.

DOI:10.1371/journal.ppat.1010885

PMID:36194628

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9565686/

Abstract

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.

摘要

在存在针对 SARS-CoV-2 刺突（S）糖蛋白的预先存在免疫记忆的情况下，增强反应的最佳疫苗接种策略是全球公共卫生的一个重要问题。为了解决这个问题，我们研究了新型自我扩增 RNA（saRNA）疫苗接种后再接种英国授权的 mRNA 疫苗（BNT162b2）对有和没有既往 COVID-19 的个体的 SARS-CoV-2 特异性体液和细胞免疫反应，并将这些反应与仅接种授权疫苗的个体进行了比较。作为 COVAC1 临床试验的一部分，招募了 35 名接受 saRNA（saRNA 组）的受试者和另外 40 名仅接受授权 SARS-CoV-2 疫苗的参与者（非 saRNA 组）。通过 ELISA 和针对野生型、Delta 和 Omicron 变体的假中和测定来测量抗体反应。通过 IFN-γ ELISpot 和激活诱导标志物（AIM）测定来测量细胞反应。每组大约有 50%的人在接种疫苗前有既往 COVID-19，通过 PCR 或 ELISA 上的抗体阳性来确认。所有接受 saRNA 的人随后都接受了一剂完整的授权疫苗。在基线时，大多数（83%）接受 saRNA 的 COVID-19 初治者在第二剂后血清转化，并且既往有 COVID-19 的人在接受 saRNA 疫苗接种后两周内抗体滴度增加（中位数 27 倍），但与 mRNA 疫苗接种相比，滴度较低。在第二剂授权 mRNA 疫苗接种后两周，与非 saRNA 组或 COVID-19 初治 saRNA 组相比，既往有 COVID-19 的 saRNA 组参与者的结合和中和抗体滴度显著更高。在这个组中，细胞反应再次最高，与仅接受 mRNA 疫苗接种的组相比， Spike 特异性 CD8+T 细胞的比例更高。这些发现表明，抗原暴露的增加，无论是来自自然感染还是疫苗接种，都有免疫获益，特别是在接受 saRNA 和 mRNA 异源疫苗接种的人群中更为明显。