关键词: IFNγ ELISpot assay SARS-CoV-2 T cell response anti-RBD IgG anti-S IgA anti-S1/S2 IgG breakthrough infection long-term immunity

来  源:   DOI:10.3390/vaccines12010003   PDF(Pubmed)

Abstract:
The effectiveness of COVID-19 vaccines developed against the original virus strain deteriorated noticeably in efficacy against the Omicron variant (B.1.1.529). Moreover, the immunity developed after vaccination or due to natural infection rapidly waned. In the present study, covering this period, we summarize the incidence of breakthrough infections among healthcare workers (HCWs) with respect to administration of the three vaccine doses. Additionally, we evaluate the long-term SARS-CoV-2-specific humoral and T cell responses at two different time points: six and twelve months after receipt of the third (booster) dose. The spike-protein-specific antibody levels and the quantity of structural-protein-specific T cells were evaluated at these time points and compared with the values measured earlier, 14 days after the booster vaccination. The study participants were categorized into two cohorts: Members of the first cohort received a two-dose BNT162b2 mRNA-based vaccine regimen, followed by an additional BNT162b2 booster six months later. Individuals in the second cohort received an inactivated-virus-based BBIBP-CorV booster six months after the initial two-dose BNT162b2 vaccination. Overall, 64.3% of participants were infected with SARS-CoV-2 confirmed by PCR or antigen test; however, additional subjects from the first cohort (23%) who did not know about their previous infection but had an anti-nucleocapsid T cell response were also considered virus-experienced. According to our results, no statistically significant difference was found between the two cohorts regarding the SARS-CoV-2-specific T cell response, neutralizing anti-RBD IgG, and anti-S IgA serum antibody levels either six or twelve months after receiving the booster, despite the overall higher median values of the first cohort. The only significant difference was the higher anti-S1/S2 IgG antibody level in the first cohort one year after the BNT162b2 booster (p = 0.039). In summary, the BNT162b2 and BBIBP-CorV boosters maintain durable humoral and T cell-mediated immune memory even one year after application. Although the booster provided limited protection against Omicron breakthrough infections, as 73.6% of these infections occurred after the booster vaccination, which means 53.5% cumulative incidence, it still offered excellent protection against severe disease and hospitalization in both cohorts.
摘要:
针对原始病毒株开发的COVID-19疫苗的有效性在针对Omicron变体的效力上明显下降(B.1.1.529)。此外,疫苗接种后或由于自然感染而产生的免疫力迅速减弱。在本研究中,涵盖这一时期,我们总结了医疗工作者(HCWs)中3种疫苗剂量的突破性感染发生率.此外,我们评估了两个不同时间点的长期SARS-CoV-2特异性体液和T细胞反应:接受第三次(加强)剂量后6个月和12个月.在这些时间点评估刺突蛋白特异性抗体水平和结构蛋白特异性T细胞的数量,并与之前测量的值进行比较。加强免疫后14天。研究参与者分为两个队列:第一个队列的成员接受了两剂基于BNT162b2mRNA的疫苗方案,接下来是一个额外的BNT162b2助推器六个月后。第二组中的个体在初始两剂BNT162b2疫苗接种后六个月接受基于灭活病毒的BBIBP-CorV加强剂。总的来说,64.3%的参与者感染了经PCR或抗原检测证实的SARS-CoV-2;来自第一队列(23%)的其他受试者(以前不知道他们的感染,但有抗核衣壳T细胞反应)也被认为是病毒经历.根据我们的结果,在SARS-CoV-2特异性T细胞反应方面,两组之间没有发现统计学上的显着差异,中和抗RBDIgG,和抗SIgA血清抗体水平在接受加强后六个月或十二个月,尽管第一队列的总体中位数较高.唯一的显著差异是在BNT162b2加强后一年的第一队列中更高的抗S1/S2IgG抗体水平(p=0.039)。总之,BNT162b2和BBIBP-CorV助推器即使在应用一年后仍保持持久的体液和T细胞介导的免疫记忆。尽管助推器对Omicron突破性感染的保护有限,因为73.6%的感染发生在加强疫苗接种后,这意味着53.5%的累积发病率,在这两个队列中,它仍然对严重疾病和住院提供了极好的保护。
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