SARS-CoV-2 vaccination induces immunological memory able to cross-recognize variants from Alpha to Omicron

Tarke, Alison; Coelho, Camila H.; Zhang, Zeli; Dan, Jennifer M.; Yu, Esther Dawen; Methot, Nils; Bloom, Nathaniel I.; Goodwin, Benjamin; Phillips, Elizabeth; Mallal, S.; Sidney, John; Filaci, Gilberto; Weiskopf, Daniela; Antunes, Ricardo da Silva; Crotty, Shane; Grifoni, Alba; Sette, Alessandro

doi:10.1101/2021.12.28.474333

Cited by 41 publications

(44 citation statements)

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“…However, when considering the overall response to Spike, we found that the majority of the response is conserved. Our observations are in agreement with works from other groups recently released as pre-print publications, which suggest minimal escape of T cell immunity by Omicron ( 21 – 26 ). Although it may not be sufficient alone to guarantee protection from infection, a conserved CD4+ T cell immunity against common SARS-CoV-2 VOCs may be fundamental to reduce disease severity, as demonstrated by the importance of a rapid T cell response in preventing severe COVID-19 ( 27 ).…”

Section: Discussionsupporting

confidence: 93%

SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron

et al. 2022

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Although accumulating data have investigated the effect of SARS-CoV-2 mutations on antibody neutralizing activity, less is known about T cell immunity. In this work, we found that the ancestral (Wuhan strain) Spike protein can efficaciously reactivate CD4+ T cell memory in subjects with previous Alpha variant infection. This finding has practical implications, as in many countries only one vaccine dose is currently administered to individuals with previous COVID-19, independently of which SARS-CoV-2 variant was responsible of the infection. We also found that only a minority of Spike-specific CD4+ T cells targets regions mutated in Alpha, Beta and Delta variants, both after natural infection and vaccination. Finally, we found that the vast majority of Spike-specific CD4+ T cell memory response induced by natural infection or mRNA vaccination is conserved also against Omicron variant. This is of importance, as this newly emerged strain is responsible for a sudden rise in COVID-19 cases worldwide due to its increased transmissibility and ability to evade antibody neutralization. Collectively, these observations suggest that most of the memory CD4+ T cell response is conserved against SARS-CoV-2 variants of concern, providing an efficacious line of defense that can protect from the development of severe forms of COVID-19.

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Section: Discussionsupporting

confidence: 93%

SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron

et al. 2022

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“…Finally, confirmation of our results from cohorts in other geographical areas and exposure to other vaccines would offer further reassurance of the maintenance of T cell responses against Omicron. Indeed, emerging data suggest this to be the case 25,[41][42][43][44][45] .…”

Section: Discussionmentioning

confidence: 99%

T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Keeton

Tincho

Ngomti

et al. 2022

Nature

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415

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The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9–12.

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“…Our hypothesis is supported by two recent preprint publications indicating that the majority of the T-cell response induced by vaccination or natural infection cross-recognizes the Omicron variant, thereby likely contributing to protection against severe disease. 20,21 An alternative or additional mechanism by which protection against severe disease may be conferred, despite reduced neutralizing antibody activity against the Omicron variant, is through Fc-mediated effector functions of non-neutralizing antibodies inducing antibody-mediated cellular phagocytosis, complement deposition, and natural killer cell activation. 18,22 In addition, the Omicron variant may be less potent at causing serious illness.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the extent to which the polyepitopic T-cell response induced by vaccination against the spike-protein and the even more diverse polyepitopic T-cell response stimulated by natural infection, with or without vaccination, remain cross-reactive against the Omicron variant warrants further investigation. 20,21…”

Section: Discussionmentioning

confidence: 99%

South African Population Immunity and Severe Covid-19 with Omicron Variant

Madhi

Kwatra

Myers

et al. 2021

Preprint

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Background We conducted a seroepidemiological survey from October 22 to December 9, 2021, in Gauteng Province, South Africa, to determine SARS-CoV-2 immunoglobulin G (IgG) seroprevalence primarily prior to the fourth wave of coronavirus disease 2019 (Covid-19), in which the B.1.1.529 (Omicron) variant is dominant. We evaluated epidemiological trends in case rates and rates of severe disease through to December 15, 2021, in Gauteng. Methods We contacted households from a previous seroepidemiological survey conducted from November 2020 to January 2021, plus an additional 10% of households using the same sampling framework. Dry blood spot samples were tested for anti-spike and anti-nucleocapsid protein IgG using quantitative assays on the Luminex platform. Daily case and death data, weekly excess deaths, and weekly hospital admissions were plotted over time. Results Samples were obtained from 7010 individuals, of whom 1319 (18.8%) had received a Covid-19 vaccine. Overall seroprevalence ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) in children aged <12 years to 79.7% (95% CI, 77.6 to 81.5) in individuals aged >50 years. Seropositivity was 6.22-fold more likely in vaccinated (93.1%) vs unvaccinated (68.4%) individuals. Epidemiological data showed SARS-CoV-2 infection rates increased more rapidly than in previous waves but have now plateaued. Rates of hospitalizations and excess deaths did not increase proportionately, remaining relatively low. Conclusions We demonstrate widespread underlying SARS-CoV-2 seropositivity in Gauteng Province prior to the current Omicron-dominant wave, with epidemiological data showing an uncoupling of hospitalization and death rates from infection rate during Omicron circulation.

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SARS-CoV-2 vaccination induces immunological memory able to cross-recognize variants from Alpha to Omicron

Cited by 41 publications

References 44 publications

SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron

SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron

T cell responses to SARS-CoV-2 spike cross-recognize Omicron

South African Population Immunity and Severe Covid-19 with Omicron Variant

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