T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents

Schiavoni, Ilaria; Palmieri, Annapina; Olivetta, Eleonora; Leone, Pasqualina; Lonardo, Anna Di; Mazzoli, Alessandra; Cafariello, Carmine; Palamara, Anna Teresa; Incalzi, Raffaele Antonelli; Onder, Graziano; Stefanelli, Paola; Fedele, Giorgio; Amici, Lucia; Berardi, F; Bernardi, Riccardo; Cardillo, Mario; Cobani, Anila; Confessore, Ida; Fiorucci, Claudia; Guerriero, Serena; Kountsevitch, Liudmila; Leccese, Vincenzo; Ruocco, Federica; Sabino, Pasquale; Sciarretta, Antonio; Spaccaferro, Deborah; Spinelli, Luciana S.; Ursino, R; Viotti, Romina

doi:10.1016/j.jamda.2022.11.024

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…We observed a lower magnitude of pro-in ammatory spike-speci c T-cell responses in LTCF residents and outpatients than in healthcare workers following primary vaccination, suggesting that the level of cell-mediated immunity following COVID-19 vaccination in older and more vulnerable individuals may be lower than that in healthy younger populations. These ndings align with those of previous studies reporting diminished T-cell reactions in older individuals (12,(42)(43)(44)(45). Although mortality rates from COVID-19 have decreased to levels comparable to those of in uenza in younger individuals, they are still higher in older individuals (2).…”

Section: Discussionsupporting

confidence: 90%

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

Kakugawa,

Mimura,

Mimura-Kimura

et al. 2024

Preprint

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Background The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, this 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific T-cell responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. CD4 + T-cell responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions Older and severely frail individuals may exhibit diminished cell-mediated immune responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that of the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.

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Section: Discussionsupporting

confidence: 90%

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

Kakugawa,

Mimura,

Mimura-Kimura

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The boosted response considered by the authors has not yet been complicated by the large heterogeneity in the immune imprinting of different individuals, which has been delineated in subsequent studies [7], showing the importance of temporal sequences of viral variant infection and vaccination for long-lasting cross-reactive protection. A previous study on booster vaccine doses in nursing home residents in Italy has shown similar results, with boosted restoration of spike-specific T cell responses in SARS-CoV-2 naive residents who responded poorly to the first immunization, while those with a previous infection had a major increase in the magnitude of vaccine-induced cell-mediated immunity, and at earlier time points [8]. The group in Freiburg, together with others, has already reported that booster vaccination increased the breadth of the spike-specific T cell response in convalescent individuals but not in vaccinees with complete initial vaccination; however, in both, the targeted T cell epitopes were broadly conserved [9].…”

Section: Boosting T Responsessupporting

confidence: 62%

When Cell-Mediated Immunity after Vaccination Is Important

Paganelli

2024

Pathogens

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“…These findings align with those of previous studies employing various methodologies such as measurement of cytokine levels in cell culture supernatants, ELISpot or FluoroSpot T-cell assays, and intracellular cytokine staining using flow cytometry. These studies have consistently reported diminished T-cell reactions in older individuals [ 12 , 48 – 51 ]. It is important to note that our data represent cytokine levels measured in the supernatants of spike protein peptide-stimulated PBMCs, which may include contributions from multiple cell types and not exclusively T-cells.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of pro- and anti-inflammatory spike-specific cellular immune responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: a prospective longitudinal study in Japan

Kakugawa,

Mimura,

Mimura-Kimura

et al. 2024

Immun Ageing

View full text Add to dashboard Cite

Background The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.

show abstract

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents

Cited by 11 publications

References 29 publications

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

When Cell-Mediated Immunity after Vaccination Is Important

Kinetics of pro- and anti-inflammatory spike-specific cellular immune responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: a prospective longitudinal study in Japan

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