Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses.
Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses.
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DOI：
10.3389/fimmu.2022.981350
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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事实证明，接种SARS-CoV-2疫苗是控制新冠肺炎大流行的最有效措施。接种加强疫苗时，对其需要和对免疫的影响了解有限。测定二针免疫后特异性T细胞、抗体和中和的持续时间，评估第三针免疫对获得性免疫的影响，并探讨其对突破性感染的保护作用。对77名医务人员进行为期12个月的纵向评估，评估由两剂BNT162b2疫苗和第三剂mRNA-1273疫苗引发的SARS-CoV-2特异性T细胞、免疫球蛋白和中和抗体，其中17名医务人员在接种疫苗前感染SARS-CoV-2(康复)，60名未接种疫苗。细胞和体液反应在第二次注射后2周达到峰值。此后抗体下降，而T细胞在接种后3个月达到平台期。中和力的下降在幼稚的个体中尤为明显，正是这一群体从第三剂疫苗中受益最大，导致中和力增加了20.9倍。总体而言，康复的人在接种疫苗后1至6个月保持了比幼稚更高的T细胞、抗体和中和水平。17例无症状或轻微的SARS-CoV-2突破性感染在随访期间被报告，仅发生在幼稚的个人中。这种病毒暴露增强了适应性免疫力。疫苗接种后15天T细胞和中和抗体水平高峰值与预防突破性感染有关。在幼稚的人中加强疫苗接种，并在未来的疫苗配方中包括除SPEKE以外的病毒抗原，可能是防止SARS-CoV-2突破性感染的有用策略。
SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity. To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection. 12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve. Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections. Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.