Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults

Samandari, Taraz; Ongalo, Joshua; McCarthy, Kimberly J.; Biegon, Richard K; Madiega, Philister Adhiambo; Mithika, Anne; Orinda, Joseph O.; Mboya, Grace M; Mwaura, Patrick; Anzala, Omu; Onyango, Clayton; Oluoch, Fredrick O; Osoro, Eric; Dutertre, Charles‐Antoine; Tan, Natalie Woon Hui; Hang, Shou Kit; Hariharaputran, Smrithi; Lye, David Chien; Herman‐Roloff, Amy; Bert, Nina Le; Bertoletti, Antonio

doi:10.1172/jci170011

Cited by 10 publications

(13 citation statements)

References 55 publications

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“…Of asymptomatic infection episodes identified, 36.7% only had serological evidence of infection, whereas 43.3% only had nucleocapsid (N)-specific T cell responses (Extended Data Fig. 4a ), confirming the previously reported importance of using both criteria to identify asymptomatic infections 9 – 11 . The trend of N-reactive T cell responses of asymptomatically infected children was similar to those symptomatically infected (Extended Data Fig.…”

Section: Resultssupporting

confidence: 78%

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

Zhong,

Kang,

Tay

et al. 2024

Nat Med

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The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5–12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children.

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Section: Resultssupporting

confidence: 78%

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

Zhong,

Kang,

Tay

et al. 2024

Nat Med

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“…Of asymptomatic infection episodes identi ed, 36.7% only had serological evidence of infection, while 43.3% only had N-speci c T cell responses (Extended Data Fig. 4A), con rming the previously reported importance of using both criteria to identify asymptomatic infections [9][10][11] . The trend of N-reactive T cell responses of asymptomatically infected children was similar to those of symptomatically infected (Extended Data Figs.…”

Section: Hybrid Immunity In Childrensupporting

confidence: 77%

“…Subsequently, concentrations of each cytokine in all culture supernatants were transformed using the logical transformation function, and UMAP was run using a 15 nearest neighbours (nn), min_dist of 0.2, and Euclidean distance. The results obtained from UMAP analysis were incorporated as additional parameters and converted to FCS les, which were then loaded into FlowJo to generate heatmaps of cytokine secretion on the reduced dimensions 9,10 .…”

Section: Neutralising Antibodies Against Wuhan-hu-1 and Variants Of C...mentioning

confidence: 99%

“…Identi cation of asymptomatic COVID-19 infections N-speci c antibodies, anti-S IgG, as well as N-reactive T cell responses, were used to identify subjects who were asymptomatically infected. N-reactive T cell responses were selected as a large proportion of COVID-convalescent individuals develop T cell responses against N, and its absence among prepandemic donor samples demonstrates its low cross-reactivity with seasonal coronaviruses 9,11 . At each time point, any 1) newly positive anti-N antibodies, 2) 4-fold rise in anti-S IgG in the absence of vaccination, or 3) signi cant increase in IFN-g or interleukin-2, were taken to represent an interim asymptomatic SARS-CoV-2 infection.…”

Section: Isolation Of Peripheral Blood Mononuclear Cells (Pbmcs)mentioning

confidence: 99%

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Longitudinal adaptive immune profiling of vaccinated children reveals correlates of protection against symptomatic SARS-CoV-2 infection

Youjia,

Kang,

Tay

et al. 2023

Preprint

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The development of evidence-based COVID-19 vaccination policies for new birth cohorts is hindered by the lack of systematic examination of the protective capacity of elements of adaptive immunity besides neutralising antibodies. To address this knowledge gap, we conducted a longitudinal cohort study of healthy 5- to 12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralising antibody titres, Spike (S)-specific memory B cell (MBC) and S-reactive T cell responses over 1 year; SARS-CoV-2 infections were ascertained using antigen rapid tests, and serological and cellular responses against nucleocapsid. We found that children mounted antibody, MBC and T cell responses after 2 doses, with continual expansion of SARS-CoV-2 variant neutralising capacity up to 1 year in the absence of wild-type infection. A booster (third) dose only improved neutralising antibody titres without impacting MBC and T cell responses. Hybrid immunity was greater in those infected after 2 vaccine doses than those infected before dose 2. Binding IgG titres, MBC and T cell responses were predictive of protection against symptomatic infection prior to attaining hybrid immunity; neutralising antibody titres only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when antibody levels wane.

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“…40 Conversely, the persistence of cellular response to two or more viral antigens beyond the duration of antibody response has been suggested as a more reliable indicator of past exposure to SARS-CoV-2. 8,9,41 Notably, preexisting immunity from exposure to common cold coronaviruses has typically been linked to cellular responses to single SARS-CoV-2 antigens. 42 In our study, we contended that prior asymptomatic exposure to SARS-CoV-2 in patients with T1D, even with negative Unfortunately, due to the limited PBMC availability, we could not directly confirm T cell cross-reactivity towards both types of peptides, such as using tetramers loaded with different fluorophores.…”

Section: Discussionmentioning

confidence: 99%

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Palmieri,

Santamaria,

Cristiani

et al. 2024

Diabetes Metabolism Res

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AimsIndividuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID‐19). Pre‐existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS‐CoV‐2 antigens in unexposed patients with T1D.Materials and methodsPeripheral blood mononuclear cells (PBMCs) were collected from SARS‐CoV‐2 unexposed patients with T1D and healthy control subjects. SARS‐CoV‐2 specific T cells were identified in PBMCs by ex‐vivo interferon (IFN)γ‐ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis.ResultsT1D patients unexposed to SARS‐CoV‐2 exhibited higher rates of virus‐specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT‐8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT‐8 autoantigens.ConclusionsThe increased frequency of SAR‐CoV‐2‐ reactive T cells in T1D patients might protect against severe COVID‐19 and overt infections. These results emphasise the long‐standing association between viral infections and T1D.

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Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults

Cited by 10 publications

References 55 publications

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

Longitudinal adaptive immune profiling of vaccinated children reveals correlates of protection against symptomatic SARS-CoV-2 infection

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

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