We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4 + ) and 87% (CD8 + ) of memory T cell responses were preserved against variants on average by AIM assay, and 84% (CD4 + ) and 85% (CD8 + ) preserved against Omicron. Omicron RBD memory B cell recognition was substantially reduced to 42% compared to other variants. T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4 + and CD8 + T cells, with average preservation > 80% for Omicron. Functional preservation of the majority of T cell responses may play an important role as second-level defenses against diverse variants.

Highlights d T cell responses recognize at least 30-40 epitopes in each donor d Immunodominance is correlated with HLA binding d Immunodominant regions for CD4 + T cells have minimal overlap with antibody epitopes d CD8 + T cell responses depend on the repertoire of HLA class I alleles

Highlights d T cells of exposed donors or vaccinees effectively recognize SARS-CoV-2 variants d Effective recognition in AIM and FluoroSPOT assays, for spike and other proteins d 93% and 97% of CD4 and CD8 epitopes are 100% conserved across variants

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

SUMMARYT cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens, and precisely measure virus-specific CD4+ and CD8+ T cells, we studied epitope-specific T cell responses of approximately 100 convalescent COVID-19 cases. The SARS-CoV-2 proteome was probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of HLA alleles for class II responses. For HLA class I, we studied an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identified several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance were observed, which differed for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes were combined into new epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells.

SUMMARYWe address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.

Background Our laboratory published the first evidence that nutritional ketosis, induced by ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in PKD animal models. We reasoned that, due to their frequent use for numerous health benefits, some ADPKD patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect first real-life observations of ADPKD patients about safety, feasibility, and possible benefits of KDIs in ADPKD as part of a translational project pipeline. Methods Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects, the feasibility and safety of KDIs in questionnaire-based interviews. Results 131 ADPKD patients took part in this study. 74 executed a KD and 52 TRD, for 6 months on average. 86% of participants reported that KDIs had improved their overall health. 67% described improvements in ADPKD-associated health issues. 90% observed significant weight loss. 64% of participants with hypertension reported improvements in blood pressure. 66% noticed adverse effects that are frequently observed with KDIs. 22 participants reported safety concerns like hyperlipidemia. 45 participants reported slight improvements in eGFR. 92% experienced KDIs as feasible while 53% reported breaks during their diet. Discussion Our preliminary data indicate that KDIs may be safe, feasible, and potentially beneficial for ADPKD patients highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.

The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4+ T cell responses widely cross-recognizing different CoVs, we utilized samples collected pre-pandemic to systematically analyze T cell reactivity against representative alpha (NL63) and beta (OC43) common cold CoVs (CCC). Similar to previous findings on SARS-CoV-2, the S, N, M, and nsp3 antigens were immunodominant for both viruses while nsp2 and nsp12 were immunodominant for NL63 and OC43, respectively. We next performed a comprehensive T cell epitope screen, identifying 78 OC43 and 87 NL63-specific epitopes. For a selected subset of 18 epitopes, we experimentally assessed the T cell capability to cross-recognize sequences from representative viruses belonging to alphaCoV, sarbecoCoV, and beta-non-sarbecoCoV groups. We found general conservation within the alpha and beta groups, with cross-reactivity experimentally detected in 89% of the instances associated with sequence conservation of >67%. However, despite sequence conservation, limited cross-reactivity was observed in the case of sarbecoCoV (50% of instances), indicating that previous CoV exposure to viruses phylogenetically closer to this subgenera is a contributing factor in determining cross-reactivity. Overall, these results provided critical insights in the development of future pan-CoV vaccines.