SARS-CoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals

Lang‐Meli, Julia; Luxenburger, Hendrik; Wild, Katharina; Karl, Vivien; Oberhardt, Valerie; Alizei, Elahe Salimi; Graeser, Anne; Reinscheid, Matthias; Roehlen, Natascha; Reeg, David B.; Giese, Sebastian; Ciminski, Kevin; Götz, Veronika; August, Dietrich; Rieg, Siegbert; Waller, Christiane; Wengenmayer, Tobias; Staudacher, Dawid L.; Huzly, Daniela; Bengsch, Bertram; Kochs, Georg; Schwemmle, Martin; Emmerich, Florian; Böettler, Tobias; Thimme, Robert; Hofmann, Maike; Neumann‐Haefelin, Christoph

doi:10.1038/s41564-022-01106-y

Cited by 31 publications

(31 citation statements)

References 14 publications

(16 reference statements)

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“…Further, broad viral reactivity, with similar levels of cytokine-production were observed following stimulation with WH-01, Beta, Delta, and Omicron epitopes. This is consistent with epitope-mapping studies of human RBD-specific T cell responses showing that while viral variants commonly develop point mutations associated with partial evasion of antibody neutralization, most T cell-specific epitopes are maintained, representing a more consistent target for durable immune recognition 41 .…”

Section: Discussionsupporting

confidence: 85%

Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates

Seenappa

Jakubowski

Steinbuck

et al. 2022

Preprint

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Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.

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Section: Discussionsupporting

confidence: 85%

Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates

Seenappa

Jakubowski

Steinbuck

et al. 2022

Preprint

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“…First, we analyzed the kinetics of the spike-specific CD8 + T cell response targeting the A*01/S 865 ( n = 7) or A*02/S 269 epitope ( n = 8). A*01/S 865 - and A*02/S 269 -specific CD8 + T cells are part of a broader CD8 + T cell response targeting the spike protein after mRNA vaccination and dominant with respect to the restricting HLA class I allele 3 , 10 . The targeted epitopes are highly conserved in all VOCs, including the Omicron variants BA.1 and BA.2 (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation

et al. 2022

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Immunization with two mRNA vaccine doses elicits robust spike-specific CD8+ T cell responses, but reports of waning immunity after COVID-19 vaccination prompt the introduction of booster vaccination campaigns. However, the effect of mRNA booster vaccination on the spike-specific CD8+ T cell response remains unclear. Here we show that spike-specific CD8+ T cells are activated and expanded in all analyzed individuals receiving the 3rd and 4th mRNA vaccine shots. This CD8+ T cell boost response is followed by a contraction phase and lasts only for about 30-60 days. The spike-specific CD8+ T memory stem cell pool is not affected by the 3rd vaccination. Both 4th vaccination and breakthrough infections with Delta and Omicron rapidly reactivate CD8+ T memory cells. In contrast, neutralizing antibody responses display little boost effect towards Omicron. Thus, COVID-19 mRNA booster vaccination elicits a transient T effector cell response while long-term spike-specific CD8+ T cell immunity is conserved to mount robust memory recall targeting emerging variants of concern.

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“…This suggests that the spike-specific T-cell epitope repertoires induced after infection differ from those elicited upon mRNA vaccination. In another study, it was shown that spike-derived epitopes were not dominantly targeted in convalescent individuals compared with non-spike epitopes [ 38 ]. Therefore, immunogenic proteins other than spike, which are not addressed in this study, with fewer mutations in the Omicron BA.1 variant, may contribute to conserved-memory T-cell responses in naturally infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

Emmelot

Vos

Boer

et al. 2022

Viruses

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Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern.

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SARS-CoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals

Cited by 31 publications

References 14 publications

Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates

Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates

COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals

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