The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

Saggau, Carina; Martini, Gabriela Rios; Rosati, Elisa; Meise, Silja; Messner, Berith; Kamps, Ann-Kristin; Bekel, Nicole; Gigla, Johannes Boy; Rose, Ruben; Voß, Mathias; Geisen, Ulf; Reid, Hayley M; Sümbül, Melike; Tran, Florian; Berner, Dennis Kristopher; Khodamoradi, Yascha; Vehreschild, Maria J.G.T.; Cornely, Oliver A.; Köehler, Philipp; Krumbholz, Andi; Fickenscher, Helmut; Kreuzer, Oliver P.; Schreiber, Claudia; Franke, André; Schreiber, Stefan; Hoyer, Bimba F.; Scheffold, Alexander; Bächer, Petra

doi:10.1016/j.immuni.2022.08.003

Cited by 24 publications

(12 citation statements)

References 72 publications

(121 reference statements)

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“…After adjusting for the effects of a prior COVID-19 infection, individuals with more CD8+ naïve cells trended towards improved antibody response. The certainty of these results is limited by the small study sample size; however, our findings are consistent with evidence suggesting a greater baseline population of naïve T cells predicts improved COVID-19 vaccine responses [ 74 ]. There is biological plausibility to this argument as immune-senescent changes, particularly within the repertoire of TEMRA T cells, can promote unregulated inflammatory immune responses [ 43 , 50 ].…”

Section: Discussionsupporting

confidence: 84%

“…However, T cell responses were impaired in older adults compared to younger adults, which is postulated as a contributing mechanism to severe health outcomes associated with COVID-19 disease in the aging population [ 71 – 73 ]. Furthermore, the baseline T cell memory phenotype assessed prior to COVID-19 mRNA vaccination predicts T cell responses to vaccine, with associations of impaired responses in older adults with less naïve T cells [ 74 ]. Additionally, impaired influenza vaccine responses are associated with expanded CD8+ CD28- memory T cell populations and reductions in CD4+ T follicular helper cells (T FH ) in older adults [ 43 – 46 ].…”

Section: Introductionmentioning

confidence: 99%

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Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

et al. 2023

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Background Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. Methods We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. Results Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19). Conclusions We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

et al. 2023

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“…Pre-existing immunity in the form of ChAdOx1 neutralizing antibodies is thought to be uncommon (Dicks et al, 2012, Ramasamy et al, 2020), but there has been little investigation into ChAdOx1 cross-reactive T cell memory and the consequences this could have. ChAdOx1-S vaccination has recently been shown to expand a pre-existing CD4 + memory T cell pool that also responds to the human adenovirus 5 (Ad5) hexon protein, which shares ∼80% sequence homology with the ChAdOx1 hexon protein (Saggau et al, 2022), strongly suggesting that cross-reactive T cell epitopes are shared between human adenoviruses and the ChAdOx1 viral vector. It is possible then that a proportion of the expanding cTfh cells we observe 6-7 days post-vaccination with ChAdOx1-S are human adenovirus-specific memory cells that cross-react with a component of ChAdOx1.…”

Section: Discussionmentioning

confidence: 99%

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

Ryan

Norton

McCafferty

et al. 2022

Preprint

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We longitudinally profiled immune responses in 102 adults who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) as their primary vaccinations. Bloods were collected pre-vaccination, 1-7 days after the 1st, 2nd and 3rd doses (BNT162b2 or mRNA-1273) to assess innate and early adaptive responses, and ~28 days after the 2nd and 3rd doses to assess immunogenicity. Using a multi-omics approach including RNAseq, cytokine multiplex assay, proteomics, lipidomics, and flow cytometry we identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

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“…To date, multiple studies have shown that COVID-19 vaccination elicits a stable and fully functional CD4 + and CD8 + T cell response that is maintained across different vaccine platforms (e.g. mRNA-1237, BNT162b2m Ad26.CoV2.S and NVX-CoV2373) and VOCs (14,15,(18)(19)(20)(21)(22)(23)(24)(25)(26). For instance, boost vaccination with BNT162b2 generated highly differentiated effector CD8 + T cells and mobilized a vigorous CD8 + T cell response, at times when NAb detection was low (27).…”

Section: Introductionmentioning

confidence: 99%

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

et al. 2022

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With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old’s working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

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The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

Cited by 24 publications

References 72 publications

Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

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