Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity

Scurr, Martin; Lippiatt, George; Capitani, Lorenzo; Bentley, Kirsten; Lauder, Sarah N.; Smart, Kathryn; Somerville, Michelle; Rees, Tracey; Stanton, Richard J.; Gallimore, Awen; Hindley, James P.; Godkin, Andrew

doi:10.1038/s41467-022-32985-8

Cited by 49 publications

(32 citation statements)

References 30 publications

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“…Limitation in blood volume obtained from adolescents precluded us from detecting small differences in some outcomes between adults and adolescents, yet most of our outcomes tested satisfied non-inferiority testing, demonstrating that diverse immune responses in adults and adolescents were not different by a clinically significant margin. Because of the critical roles of T helper (Th) 1 in virus controlling 42 and the limitation of blood volume obtained from adolescents, we focused our efforts on quantifying post-vaccine Th1 T cell responses. Previously, in an adult vaccine study, we found that Spike-specific IL-4 + Th2 responses are not boosted by two-dose BNT162b2 vaccination, and the majority of post-vaccine responses were IFN-γ + T effector memory responses.…”

Section: Discussionmentioning

confidence: 99%

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

Cohen

Leung

et al. 2022

Sig Transduct Target Ther

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The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

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Section: Discussionmentioning

confidence: 99%

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

Cohen

Leung

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

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“…Elevated serum cytokine levels are associated with severe COVID-19 infections and are a strong predictor of adverse disease outcomes 19 . Adaptive immune responses, including the development of a coordinated SARS-CoV-2-specific CD4 + and CD8 + T cell response and neutralizing antibodies, are associated with a reduction in COVID-19 disease severity 20 – 22 ; however, certain T cell responses including unconventional CD16 + T cells 23 , mucosal-associated invariant T (MAIT) cells 24 and γδ T cells 25 may be increased in severe COVID-19 and are potentially related to immunopathology.…”

Section: Introductionmentioning

confidence: 99%

The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

et al. 2022

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Pre-existing cross-reactive immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in infection-naive subjects have been described by several studies. In particular, regions of high homology between SARS-CoV-2 and common cold coronaviruses have been highlighted as a likely source of this cross-reactivity. However, the role of such cross-reactive responses in the outcome of SARS-CoV-2 infection and vaccination is currently unclear. Here, we review evidence regarding the impact of pre-existing humoral and T cell immune responses to outcomes of SARS-CoV-2 infection and vaccination. Furthermore, we discuss the importance of conserved coronavirus epitopes for the rational design of pan-coronavirus vaccines and consider cross-reactivity of immune responses to ancestral SARS-CoV-2 and SARS-CoV-2 variants, as well as their impact on COVID-19 vaccination.

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“…Despite such evidence, epidemiological assessments of the prevalence of SARS-CoV-2 have mainly utilized serologic assays since antibodies are easier to measure than T cells responses. However, methodologies to rapidly detect virus-specific T cell responses flourished during the COVID-19 pandemic 21,[35][36][37] , including the use of whole blood which appeared to correlate with protection from SARS-CoV-2 infection in one study 37 . Here, we show directly that cytokine detection following whole blood stimulation with peptides can be implemented in locations within a few hours distance from a facility with biosafety level-1 cabinets.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory SARS-CoV-2 T cell immunity in asymptomatic seronegative Kenyan adults

Samandari

Ongalo

McCarthy

et al. 2023

Preprint

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Antibodies are used to estimate prevalence of past infection. However, T cell responses against SARS-CoV-2 may more accurately define prevalence because SARS-CoV-2-specific antibodies wane. In November-December 2021, we studied serological and cellular immune responses in residents of rural Kenya who had not experienced any respiratory symptom nor had contact with COVID-19 cases. Among participants we detected anti-spike antibodies in 41.0% and T cell responses against ≥2 SARS-CoV-2 proteins in 82.5%, which implies that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. Distinct from cellular immunity in European and Asian COVID-19 convalescents, strong T cell immunogenicity was observed against viral accessory proteins in these asymptomatic Africans, as well as a higher IL-10/IFN-γ ratio cytokine profile, suggesting that environmental or genetic factors modulate pro-inflammatory responses.

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Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity

Cited by 49 publications

References 30 publications

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

Anti-inflammatory SARS-CoV-2 T cell immunity in asymptomatic seronegative Kenyan adults

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