PDF(Pubmed)
Abstract：
UNASSIGNED: Accumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs.
UNASSIGNED: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs.
UNASSIGNED: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination.
UNASSIGNED: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.
UNASSIGNED: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs.
UNASSIGNED: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination.
UNASSIGNED: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.
摘要：
■越来越多的证据表明T细胞免疫在疫苗接种诱导的针对严重COVID-19疾病的保护中的重要性，特别是针对SARS-CoV-2关注变体（VOC），更容易通过中和抗体逃避识别。然而,对不同年龄组的T细胞应答以及使用不同疫苗组合进行初次和加强疫苗接种后CMV状态的影响的了解有限.此外，目前尚不清楚年龄是否影响T细胞对VOCs的交叉反应能力.
■因此，我们调查了不同年龄的荷兰人的健康成年人的Spike特异性T细胞反应，他们接受了不同类型的疫苗进行主要系列和/或加强疫苗接种，使用IFNELISpot。用祖先刺突蛋白和不同VOC的重叠肽库刺激细胞。
■在初次疫苗接种系列的绝大多数参与者中检测到了稳健的Spike特异性T细胞应答，无论疫苗类型(即BNT162b2、mRNA-1273、ChAdOx1nCoV-19或Ad26。COV2.S).显然,在70岁以上的年龄组中，与年轻年龄组相比,反应总体较低,差异较大.仅在CMV血清阳性的老年人（>70岁）中，年龄与T细胞反应呈显着的负相关。尽管加强疫苗接种后所有年龄组的T细胞反应均增加，在70岁以上的年龄组中，Spike特异性T细胞频率仍然较低。无论年龄或CMV状态，与BNT162b2/BNT162b2或BNT162b2/mRNA-1273初级加强方案相比，初级mRNA-1273疫苗接种和BNT162b2加强疫苗接种显示出有限的加强效果。与α的交叉反应性适度降低，Delta和OmicronBA.1，但不是Beta或Gamma变体，在初次接种疫苗后观察到。
■一起，这项研究表明，年龄，CMV状态,而且初级加强疫苗接种方案也会影响疫苗接种诱导的Spike特异性T细胞反应的高度，但不影响VOC交叉反应性。
■因此，我们调查了不同年龄的荷兰人的健康成年人的Spike特异性T细胞反应，他们接受了不同类型的疫苗进行主要系列和/或加强疫苗接种，使用IFNELISpot。用祖先刺突蛋白和不同VOC的重叠肽库刺激细胞。
■在初次疫苗接种系列的绝大多数参与者中检测到了稳健的Spike特异性T细胞应答，无论疫苗类型(即BNT162b2、mRNA-1273、ChAdOx1nCoV-19或Ad26。COV2.S).显然,在70岁以上的年龄组中，与年轻年龄组相比,反应总体较低,差异较大.仅在CMV血清阳性的老年人（>70岁）中，年龄与T细胞反应呈显着的负相关。尽管加强疫苗接种后所有年龄组的T细胞反应均增加，在70岁以上的年龄组中，Spike特异性T细胞频率仍然较低。无论年龄或CMV状态，与BNT162b2/BNT162b2或BNT162b2/mRNA-1273初级加强方案相比，初级mRNA-1273疫苗接种和BNT162b2加强疫苗接种显示出有限的加强效果。与α的交叉反应性适度降低，Delta和OmicronBA.1，但不是Beta或Gamma变体，在初次接种疫苗后观察到。
■一起，这项研究表明，年龄，CMV状态,而且初级加强疫苗接种方案也会影响疫苗接种诱导的Spike特异性T细胞反应的高度，但不影响VOC交叉反应性。
