Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination

Gao, Yu; Cai, Curtis; Wullimann, David; Nießl, Julia; Rivera‐Ballesteros, Olga; Chen, Puran; Lange, John R.; Cuapio, Angélica; Blennow, Ola; Hansson, Lotta; Mielke, Stephan; Nowak, Piotr; Vesterbacka, Jan; Akber, Mira; Perez‐Potti, André; Sekine, Takuya; Müller, Thomas; Boulouis, Caroline; Kammann, Tobias; Parrot, Tiphaine; Muvva, Jagadeeswara Rao; Sobkowiak, Michał J.; Healy, Katie; Bogdanović, Gordana; Muschiol, Sandra; Söderdahl, Gunnar; Österborg, Anders; Hellgren, Fredrika; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Loré, Karin; Chen, Margaret Sällberg; Ljungman, Per; Sandberg, Johan K.; Smith, C.; Bergman, Peter; Ljunggren, Hans‐Gustaf; Aleman, Soo; Buggert, Marcus

doi:10.1016/j.immuni.2022.07.005

Cited by 56 publications

(91 citation statements)

References 60 publications

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“…Overall, our analysis of the global T cell profile of individuals with low/absent nAbs but detectable functional T cell responses revealed that reduced availability of T FH cells could contribute to the serological defect observed in conjunction with the previously highlighted imbalance in MBCs. Moreover, we have identified a subset of CD8 T cells that is overrepresented in PLWH with low/absent nAbs and may enable stronger functional T cell responses, supported by recent findings showing that CXCR3 + CD8 T cells are polyfunctional and associated with survival in critical SARS-CoV-2 patients, and have been observed in other immunosuppressed groups (Adam et al, 2021; Gao et al, 2022).…”

Section: Resultssupporting

confidence: 85%

“…Despite these caveats, our study provides new insights into the reasons why some PLWH fail to produce effective humoral responses, and an in-depth assessment of B cell responses. The observation of a more abundant CD8 T cell profile in some PLWH with absent or low-level antibody responses supports the notion that virus-specific CD8 T cells could compensate for defects in humoral immunity after SARS-CoV-2 vaccination in PLWH, as previously described for other immunocompromised groups (Gao et al, 2022). Overall, our data supports the benefit of a third SARS-CoV-2 dose in inducing nAbs against Omicron in PLWH, as it does in the general population.…”

Section: Discussionsupporting

confidence: 89%

“…This phenotype was not clearly related to HIV parameters or presence of co-morbidities. These T cell populations have been linked with increased survival in people infected with SARS-CoV-2 and are consistent with observations in patient groups who lack B cell responses (Gao et al, 2022). Upregulation of CXCR3 in vaccine-induced T cells with potential to home to lung mucosa in tuberculosis (Jeyanathan et al, 2017) suggests that these CD8 T cells described herein could play a role in the protection against severe respiratory diseases such as SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 88%

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Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

Touizer

Alrubbayi

Ford

et al. 2022

Preprint

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People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+ T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.

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Section: Resultssupporting

confidence: 85%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

Touizer

Alrubbayi

Ford

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…T cells are thought to maintain protection against SARS-CoV-2 infection when neutralizing antibody levels wane over time 31 . We therefore considered the single cell T cell and innate lymphocyte transcriptomes in isolation, comprising 72,507 cells, including naïve, effector memory (EM), terminal effector (TE) and cytotoxic CD4 T cells and naïve, EM and TE CD8 T cells, as well as CD16+ and CD56+CD16-NK cells, ILCs, MAITs, NKT and □ □T cells ( Figure 4A-B ).…”

Section: Resultsmentioning

confidence: 99%

Atypical B cells and impaired SARS-CoV-2 neutralisation following booster vaccination in the elderly

Ferreira

Lee

Foster

et al. 2022

Preprint

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Age is a major risk factor for hospitalization and death after SARS-CoV-2 infection, even in vaccinees. Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here we show that individuals 70 or older who received a primary two dose schedule with AZD1222 and booster third dose with mRNA vaccine achieved significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared to those younger than 70. One month after the booster neither the concentration of serum binding anti spike IgG antibody, nor the frequency of spike-specific B cells showed differences by age grouping. However, the impaired neutralization potency and breadth post-third dose in the elderly was associated with enrichment of circulating atypical spike-specific B cells expressing CD11c and FCRL5. Single cell RNA sequencing confirmed an expansion of TBX21-, ITGAX-expressing B cells in the elderly that enriched for B cell activation/receptor signalling pathway genes. Importantly we also observed impaired T cell responses to SARS-CoV-2 spike peptides in the elderly post-booster, both in terms of IFNgamma and IL2 secretion, as well as a decrease in T cell receptor signalling pathway genes. This expansion of atypical B cells and impaired T cell responses may contribute to the generation of less affinity-matured antibodies, with lower neutralizing capacity post-third dose in the elderly. Altogether, our data reveal the extent and potential mechanistic underpinning of the impaired vaccine responses present in the elderly after a booster dose, contributing to their increased susceptibility to COVID-19 infection.

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“…IEI patients show a variably reduced response to vaccinations [25,29,30] in terms of antibody production and specific immune cell activation and we may speculate that they probably also exhibit fewer symptoms and adverse events than the general population, due to their immune underlying defect. This is also highlighted by a recent Hungarian study, testing specific antibody and the T cell response elicited by BNT162b2 boosting after two ChAdOx1 shots in a cohort of CVID patients, compared with healthy control subjects.…”

Section: Discussionmentioning

confidence: 99%

Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

et al. 2022

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Purpose Little is known about vaccine safety in inborn errors of immunity (IEI) patients during the current vaccination campaign for COVID-19. To better investigate the reactogenicity and adverse event profile after two, three, and four doses of mRNA vaccines, we conducted an observational, multicentric study on 342 PID patients from four Italian Referral Centres. Methods We conducted a survey on self-reported adverse reactions in IEI patients who received mRNA vaccine by administering a questionnaire after each dose. Results Over the whole study period, none of the patients needed hospitalization or had hypersensitivity reactions, including anaphylaxis and delayed injection site reaction. After two vaccination doses, 35.4% of patients showed only local reactogenicity-related symptoms (RrS), 44.4% reported both systemic and local RrS, and 5% reported only systemic RrS. In more than 60% of cases, local or systemic RrS were mild. After the first and second booster doses, patients showed fewer adverse events (AEs) than after the first vaccination course. Patients aged 50 years and older reported adverse events and RrS less frequently. Among AEs requiring treatment, one common variable immune deficiency patient affected by T cell large granular lymphocytic leukemia developed neutropenia and one patient had Bell’s paralysis perhaps during herpes zoster reactivation. Conclusion Although our follow-up period is relatively short, the safety data we reported are reassuring. This data would help to contrast the vaccine hesitancy often manifested by patients with IEI and to better inform their healthcare providers.

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Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination

Cited by 56 publications

References 60 publications

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

Atypical B cells and impaired SARS-CoV-2 neutralisation following booster vaccination in the elderly

Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

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