The electrochemical properties of layered vanadate cathode materials for aqueous zinc ion batteries (AZIBs) are still restricted by sluggish reaction kinetics, low conductivity, and poor structural stability. Herein, the Na-doped hydrated NH4V4O10 (NaNVOH) with different contents of interlayered H2O/NH4+ and O-vacancies are obtained with optimized electrostatic interaction between [VOn] framework and H2O/NH4+/Na+ as well as Zn2+ diffusion kinetics. Experimental evidence and theoretical calculations show that the optimal interlayered H2O/NH4+ and more O-vacancies in NaNVOH (NaNVOH2) reinforce the bond strength, narrow the band gap, and promote Zn2+ diffusion coefficients. The reduced H+ insertion hinders cathode/electrolyte interfacial side reaction, ensures sufficient Zn2+ diffusion coefficients at voltage range of 0.6-0.2 V. Meantime, the high electrochemical reversibility of Zn3(OH)2V2O7 & sdot;2H2O by-product is also validated by in-situ and ex-situ characterizations. As a result, the NaNVOH2 cathode shows a high specific capacity (519 mAh g-1 at 0.5 C, 1 C = 500 mA g-1), good rate capability (236 mAh g-1 at 10 C), and a stable cycling life (without obvious capacity decay over 3000 cycles at 15 C). This study is of great significance for developing high-performance layered vanadate toward the practical application of AZIBs.

Background: T-cell receptor (TCR)-engineered T-cell therapy (TCR-T) has become a promising anticancer therapy. Recognition of tumor cells by TCR-T cells requires matched human leukocyte antigen (HLA) alleles and tumor antigens, which seriously limits their population coverage. One strategy to expand the population coverage of a specific TCR-T cell therapy is to enable TCR-T cells to recognize target peptides presented by more HLA alleles. Methods: In this study, HLA alleles were selected based on the Chinese population frequency and HLA supertype classification. Then, COS-7 and two tumor cell lines (586 mel and 5637) were transduced with selected HLA alleles for functional evaluation of TCR-T cells. HLA-A2 alleles capable of both exogenously and endogenously presenting the NY-ESO-1-derived epitope and thereby being recognized by TCR-T cells were tested. Results: We demonstrated that a given TCR-T cell product can recognize the NY-ESO-1 peptide exogenously and endogenously presented not only by HLA-A*02:01 but also by HLA-A*02:03, HLA-A*02:06, and HLA-A*02:10, almost doubling the population coverage in the Chinese population from 12.01% to 21.05%. Conclusions: Our study suggests that cancer patients expressing members of the HLA-A2 supertype may benefit from the TCR-T cell product, and other TCR-T cell products could similarly expand their population coverage even within the non-Chinese population through an analogous approach.

Layered vanadium-based compounds are promising cathode materials for aqueous zinc ion batteries (ZIBs) due to their multi-electron reactions and adjustable ion-diffusion channels. However, the narrow interplanar spacing, strong binding with Zn2+, and vanadium dissolution significantly limit their further application. Herein, we present a defective (NH4)(0.78)V4O10-x center dot 1.49H2O (N2) with a strong hydrogen bond as the cathode for ZIBs. Both experimental data and DFT calculation confirm that the triple effect of intercalating H2O, increasing oxygen defects, and introducing ammonium vacancy not only enriches the active sites but also restricts the NH4+ and vanadium by strong hydrogen bonds. Meantime, the electrostatic interaction between Zn2+ and framework is also improved, both in O-free and O-defect [VOn] polyhedrons. As expected, the N2 delivers a specific capacity of 533.1 mAh g-1 (398.2 Wh kg- 1 at 184.4 Wh kg-1) at 0.5 C, a rate-capability of 225.4 mAh g- 1 at 20 C, and without obvious capacity decay at 20 C over 2000 cycles.

Introduction GENEr8-1 (270-301; NCT03370913) is an ongoing phase 3 trial of valoctocogene roxaparvovec gene therapy for severe hemophilia A. Primary study outcomes demonstrate that valoctocogene roxaparvovec enables endogenous factor VIII (FVIII) production, reduces bleeding episodes, and reduces FVIII concentrate use versus prior FVIII prophylaxis treatment. Here, we report the procedures performed and associated FVIII use post-gene transfer with valoctocogene roxaparvovec in participants of the 301 trial.

BACKGROUND Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

Aqueous zinc-ion batteries (ZIBs) have been regarded as promising secondary batteries due to their remarkable inherent properties. As a typical layer cathode material with a high specific capacity, ammonium vanadate (NH4V4O10) still suffers from sluggish kinetics and poor electronic conductivity, which results in poor rate performance and short service life. Herein, a co-modulation technique that integrates the anchoring effect of substitutional K+ and the modulating effect of dual defects has been proposed to boost the performance of NH4V4O10 (NVO). Coupled with the theoretical calculation results, it not only buffers the dramatic structural deformation upon zinc storage but also enhances the capacitance-limited capacity and improves the electronic conductivity. Meanwhile, the stable presence of K+ and NH4+ as pillars after long cycles is also confirmed. As a result, the specific capacity of the K+-anchored NVO with high-concentration oxygen defect and proper ammonium defect content (KNVOd-2) is 350.8 mAh/g at 1C with an extraordinary energy density of 303 Wh kg- 1. The rate capability of the KNVOd-2 is a 109% increase relative to the as-obtained K+ anchored NVO without dual-defect modulation (KNVOd-1) and remains at least 55% retention after 25-times, and without obvious capacity decay at 5C over 1000 cycles. This work provides insights for using co-modulation chemistry to introduce novel properties in layered-structured materials for high-energy aqueous ZIBs.

New York-esophageal cancer 1 (NY-ESO-1) belongs to the cancer testis antigen (CTA) family, and has been identified as one of the most immunogenic tumor-associated antigens (TAAs) among the family members. Given its ability to trigger spontaneous humoral and cellular immune response and restricted expression, NY-ESO-1 has emerged as one of the most promising targets for cancer immunotherapy. Cancer vaccines, an important element of cancer immunotherapy, function by presenting an exogenous source of TAA proteins, peptides, and antigenic epitopes to CD4+ T cells via major histocompatibility complex class II (MHC-II) and to CD8+ T cells via major histocompatibility complex class I (MHC-I). These mechanisms further enhance the immune response against TAAs mediated by cytotoxic T lymphocytes (CTLs) and helper T cells. NY-ESO-1-based cancer vaccines have a history of nearly two decades, starting from the first clinical trial conducted in 2003. The current cancer vaccines targeting NY-ESO-1 have various types, including Dendritic cells (DC)-based vaccines, peptide vaccines, protein vaccines, viral vaccines, bacterial vaccines, therapeutic whole-tumor cell vaccines, DNA vaccines and mRNA vaccines, which exhibit their respective benefits and obstacles in the development and application. Here, we summarized the current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment, aiming to provide perspectives for future research.

BACKGROUND:Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously.METHODS:We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in the annualized rate of treated bleeding events at week 104 after receipt of the infusion. The pharmacokinetics of valoctocogene roxaparvovec were modeled to estimate the bleeding risk relative to the activity of transgene-derived factor VIII.RESULTS:At week 104, a total of 132 participants, including 112 with data that were prospectively collected at baseline, remained in the study. The mean annualized treated bleeding rate decreased by 84.5% from baseline (P<0.001) among the participants. From week 76 onward, the trajectory of the transgene-derived factor VIII activity showed first-order elimination kinetics; the model-estimated typical half-life of the transgene-derived factor VIII production system was 123 weeks (95% confidence interval, 84 to 232). The risk of joint bleeding was estimated among the trial participants; at a transgene-derived factor VIII level of 5 IU per deciliter measured with chromogenic assay, we expected that participants would have 1.0 episode of joint bleeding per year. At 2 years postinfusion, no new safety signals had emerged and no new serious adverse events related to treatment had occurred.CONCLUSIONS:The study data show the durability of factor VIII activity and bleeding reduction and the safety profile of valoctocogene roxaparvovec at least 2 years after the gene transfer. Models of the risk of joint bleeding suggest that the relationship between transgene-derived factor VIII activity and bleeding episodes is similar to that reported with the use of epidemiologic data for persons with mild-to-moderate hemophilia A. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).

MnO2 is a promising material for pseudocapacitor applications due to its high specific capacity and low cost, while MnO2 electrodes suffer from their low electrical and ionic conductivities. Herein, a facile and low-cost method is adopted to synthesize MnO2 - tin-doped indium oxide nanowires (ITO NWs) composite with highly ordered network structures for electrochemical supercapacitors. Such network structure can effectively decrease the ion diffusion and charge transport resistance in the electrode. The specific capacitance of bare ITO NWs is only 2.83 F g-1, thus the contribution of the matrix material to capacitance can be ignored, and the optimized MnO2 possesses a high specific capacitor of 508.54 F g-1 at the scan rate of 5 mV s-1. It is anticipated that the synthesized MnO2-ITO NWs composite will find wide applications in supercapacitors (SCs) and other devices in virtue of their outstanding characters of good conductivity, convenient synthesis.

BackgroundCoronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants. Reportedly, T cell-based immunity alone can restrict SARS-CoV-2 replication.MethodsIn this study, we identified two TCRs targeting the RNA-dependent RNA polymerase (RdRp) protein in CD8 + T cells. Functional evaluation by transducing these TCRs into CD8 + or CD4 + T cells confirmed their specificity.ResultsCombinations of inflammatory and anti-inflammatory cytokines secreted by CD8 + and CD4 + T cells can help control COVID-19 in patients. Moreover, the targeted epitope is highly conserved in all emerged SARS-CoV-2 variants, including the Omicron. It is also conserved in the seven coronaviruses that infect humans and more broadly in the subfamily Coronavirinae.ConclusionsThe pan-genera coverage of mutant epitopes from the Coronavirinae subfamily by the two TCRs highlights the unique strengths of TCR-T cell therapies in controlling the ongoing pandemic and in preparing for the next coronavirus outbreak.

The strengthening effect of particle-reinforced copper-based composites mainly depends on the interfacial bonding strength and dispersibility of the reinforcement. However, agglomeration of nanoparticles, as a bottleneck, restricts Orowan's strengthening mechanism. Different from the traditional preparation method for stacked nanoparticles, a hydrothermal method was developed to prepare interconnected bridge-like MoO2 quantum dots. Based on the interconnected structure and the brittleness of MoO2, it can be easily broken and uniformly dispersed into copper matrix during the ball milling process. Due to the dispersion strengthening effect and coherence of the interface between MoO2 and copper, these factors improve the mechanical performance of the composite material synergistically, resulting in simultaneous increases in YS (145.76 MPa), UTS (321.67 MPa), and hardness (94.79 Hv). The effectiveness of YS and UTS enhancement is 234% and 41%, respectively, while maintaining appropriate elongation (20.29%) and conductivity (94.9 IACS). MoO2 quantum dots are used for the first time in this work as particle reinforcements, and we demonstrate that the addition of oxide quantum dots to metal matrix composites can significantly enhance the mechanical properties of the composites by changing the morphology of the quantum dots.

Vanadate-based synthesis of battery electrodes has become a topic of research interest due to the high lithium storage performance. However, the rapid capacity decay seriously hinders its practical application. In order to improve the potential for Co3V2O8 (CVO) as an electrode in lithium batteries, a Na5V12O32 nanowire precursor with a smooth surface was obtained using the hydrothermal method. Next, the CVO nanowires assembled by nanosheets were fabricated by cation exchange from the Na5V12O32 precursor. Finally, the elemental phosphorus-coated CVO was successfully synthesized by a custom furnace. The characterization of X-ray diffraction (XRD) and inductively coupled plasma emission spectroscopy (ICP-ES) quantified the ratio of P and CVO, and Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) revealed the presence and coverage. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) further demonstrated the existence and morphology of P and CVO. Meanwhile, electrochemical measurements illustrated the stable lithium storage and notable rate performance of the P-CVO electrode as compared to AN-CVO. The P-CVO electrode holds a higher stable cycle performance after 190 cycles, with discharge specific capacity of 415.3 mA h g−1 and capacity retention of 97% at a current density of 1.0 A g−1 (872 mA h g−1, 2.0 A g−1, 98.8%), versus AN-CVO with 320.6 mA h g−1 (capacity retention of 79.5%) after only 100 cycles. Thence, the synthetic strategy provides a potential solution to enhance the stability of electrodes for high-performance lithium-ion batteries.

In the present study, the facile hydrothermal method is used to prepare sodium vanadate (Na5V12O32) nanowire arrays to act as adsorbents for removing cationic dyes. The samples are characterized and compared using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrum, and X-ray diffraction. The adsorption quantity of methylene blue and gentian violet increases with the increase of adsorbent dose, adsorption time and initial dye concentration. Further, the adsorption kinetic and isotherm are well modeled by the Pseudo-second-order kinetic model and Langmuir isotherm model, respectively. The rate control step is administered by means of intra-particle diffusion during the adsorption process. The maximum adsorption capacities of methylene blue and gentian violet are 1249.0 and 1079.7 mg g(-1), respectively. Additionally, the maximum dye removal rates for MB and GV are 85.32 % and 84.46 % after five cycles, respectively. As such, Na5V12O32 nanowire arrays can be used as an efficient, low-cost and recyclable adsorbent for cationic dyes removed from wastewater.

T-cell receptor (TCR)-transduced T (TCR-T) cell therapy has shown promising efficacy in the clinical treatment of malignant cancers. However, the populations covered by reported TCRs are still limited. Tumor infiltrating lymphocytes (TILs) are natural reservoirs of tumor-reactive T cells and TCRs. Approaches are required for the fast and cost-effective identification of tumor-reactive TCRs from TILs. The widely employed TCR identification approaches by the clonal expansion of TILs involve a TCR singularization process for the direct pairing of TCR Vα and the Vβ chain. However, the clonal expansion of T cells is well known to require extensive time and effort due to the involvement of T cell cultures. Several single-cell multiplexing PCR methods followed by Sanger sequencing have been developed, representing a cost-effective and fast approach for single-cell TCR identification. In this study, an RNA-based preamplification step was included in the single-cell TCR sequencing, which can reduce the multiplexing PCR amplification to one round. Moreover, the cDNA product of RNA preamplification is derived from the whole genome mRNA, instead of TCR mRNA only by multiplexing primers-based DNA preamplification, which is valuable for many other analyses (e.g., phenotypic analysis) of the tumor-reactive T cells that can be correlated with the identified TCRs. The feasibility for both single α chain and dual α chain TILs of this approach highlights its potential value as a rapid and cost-effective sequencing strategy for the development of TCR-T therapies for solid cancers.

Objective: The aim was to study the benefits and risks of anti-CD19 chimeric antigen receptor (CAR) T-cells in adults with B-cell lymphoma.Methods: From October 2015 to October 2021, we treated five patients with B-cell lymphoma, comprising two with mantle cell lymphoma, one case of Burkitt lymphoma, one case of diffuse large B-cell lymphoma, and one case of chronic lymphocytic leukemia/small lymphocytic lymphoma. The patients were given the FC regimen 5 days before the infusion of anti-CD19 CAR T-cells. The median total number of CAR T-cells infusions was 350*10^6 (88*10^6–585*10^6).Results: 1) Patients who received CAR T-cell induction therapy achieved complete remission (CR) in Case 1 and Case 3 and partial remission (PR) in Case 2. Case 3’s ATM and D13S25 gene deletions were negative 42 days after CAR T-cell therapy, and molecular biology CR (mCR) and minimal residual disease (MRD) were negative for 5 years and 6 months. The patient in Case 3 was cured. 2) Case 4 patient’s TP53 gene mutation became negative 1 month after CAR T-cell therapy. MRD was negative after CAR T-cell therapy at 41 and 42 months in Cases 4 and 5, respectively. 3) Case 1∼Case 3 patients developed cytokine release syndrome (CRS) without encephalopathy syndrome, accompanied with serious adverse events. CRS can be effectively managed with tocilizumab, etanercept, glucocorticoids, and plasmapheresis.Conclusion: Anti-CD19 CAR T-cell therapy is effective in treating relapsed/refractory B-cell lymphoma, and the side effects of CAR T-cell therapy can be properly managed. CAR T-cell therapy has high efficacy and presented no side effects in the treatment of MRD in B-cell lymphoma (NCT03685786, NCT02456350).

Introduction: Rituximab maintenance (MR) after first line (1L) R-CHOP improved overall survival (OS) in mantle cell lymphoma (MCL) in clinical trials. How MR is used in routine clinical practice and the benefits of MR after 1L BR are less defined. We evaluated the real-world patterns and outcomes of MR after 1L BR/R-CHOP in a large US MCL cohort. Methods: This retrospective study included adult patients (pts) with MCL diagnosed Jan 2011-Nov 2020 in the nationwide Flatiron Health EHR-derived deidentified database. Pt characteristics, treatment (tx) patterns, real-world time to next tx (rwTTNT; 1L to subsequent tx or death), and real-world OS (rwOS) were evaluated for pts treated with 1L BR/R-CHOP ± MR (entire cohort). Given the potential for MR selection biases, analyses were performed in pts who were alive and did not initiate subsequent tx within 8 months (mos) of starting 1L BR or 6 mos of R-CHOP (MR-eligible cohort). Multivariate analyses (MVA) were performed for rwTTNT/OS on the effects of MR adjusting for age, ECOG PS, lactate dehydrogenase level, white blood cell count, and blastoid/pleomorphic and bulky disease status. Results: Among 2946 pts with documented 1L MCL tx, 86.3% were from a community oncology setting. In the entire cohort, 854 pts received BR alone (median duration of tx [mDOT]: 4.1 mos), 368 BR + MR (mDOT: 25.7 mos), 365 R-CHOP alone (mDOT: 3.5 mos), and 147 R-CHOP + MR (mDOT: 26.9 mos). Median pt age for starting 1L BR ± MR (72.8 years [yrs]) was older than R-CHOP ± MR (66.4 yrs). The 36-mo rwTTNT rate was highest with BR + MR (72%), followed by R-CHOP + MR (68%). Median rwTTNT was reached at 17.0 and 7.8 mos for BR and R-CHOP alone, respectively. In the MR-eligible cohort, 590 pts received BR alone (mDOT: 4.67 mos), 365 received BR + MR (mDOT: 25.8 mos), 207 received R-CHOP alone (mDOT: 4.0 mos), and 145 received R-CHOP + MR (mDOT: 26.9 mos). Disease characteristics of intermediate/high MCL International Prognostic Index or blastoid/pleomorphic biology were similar between BR/R-CHOP with and without MR (Table). MVA showed that MR was independently associated with longer rwTTNT (hazard ratio [HR] 0.45; 95% confidence interval [CI], 0.38-0.53; p < 0.001) and rwOS (HR 0.56; 95% CI, 0.45-0.7; p < 0.001). With estimated median follow-up of 38.9 mos (range 0.03-117.1) for BR ± MR and 64.3 mos (range 0.03-115.0) for R-CHOP ± MR, the 36-mo rwTTNT rate was 73% for BR + MR and 69% for R-CHOP + MR. Estimated median rwTTNT was reached at 36 and 21.5 mos for BR and R-CHOP alone, respectively. The 36-mo rwOS rate was 84% for BR + MR, 76% for BR alone, 89% for R-CHOP + MR, and 76% for R-CHOP alone. Conclusions: This is the largest real-world MCL cohort treated with 1L BR or R-CHOP, followed by MR. MR was associated with improved rwTTNT and rwOS. The best rwTTNT rate was seen with 1L BR + MR. The phase 3 SHINE study (NCT01776840) is evaluating the potential benefit of adding ibrutinib to BR + MR in pts with previously untreated MCL. EA – previously submitted to EHA 2021. The research was funded by: Janssen Research & Development Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract M. Wang Consultant or advisory role: AstraZeneca, Janssen Research and Development, Celgene, MORE Health, Juno Therapeutics, Bioinvent, Pharmacyclics/Janssen, Pulse Biosciences, AxImmune, Kite Pharma, Noble Insights, Guidepoint Global, Loxo Stock ownership: MORE Health Honoraria: Janssen Research and Development, DAVA Oncology, OM Pharmaceutical Industries, PeerView, Oncology business review, OncLive, Pharmacyclics, AstraZeneca and Targeted Oncology Research funding: AstraZeneca, Janssen Research and Development, Pharmacyclics, Kite Pharma, Juno Therapeutics, BeiGene, Novartis, Acerta Pharma, Oncternal Therapeutics, Amgen, BioInvent, Loxo, VelosBio, Celgene and Versastem Educational grants: Janssen Research and Development, AstraZeneca, Celgene, DAVA Oncology and OM Pharmaceutical Industries G. Salles Consultant or advisory role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Science, Genmab, Debiopharm group, VelosBio, Genmab, Bristol-Myers Squibb, BeiGene, Incyte and Miltenyi Biotec Honoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, Abbvie, and MorphoSys A. Kumar Consultant or advisory role: Kite (a Gilead company), Summit Advisory Committee and Steering Committee for MCL Registry for AstraZeneca Research funding: Abbvie, Adaptive Biotechnologies, Celgene, Pharmacyclics, Seattle Genetics, AstraZeneca and AstraZeneca advisory board K. Qi Employment or leadership position: Janssen K. Daly Employment or leadership position: Janssen L. Parisi Employment or leadership position: Janssen A. Zhu Employment or leadership position: Janssen P. Martin Consultant or advisory role: Celgene, Janssen, Bayer, Kite Pharma, BeiGene, I-Mab, MorphoSys, TeneoBio, Karyopharm Therapeutics, Kite/Gilead, Verastem, Cellectar and Regeneron Research funding: Karyopharm Therapeutics Educational grants: Janssen

BACKGROUNDCoronavirus disease-19 (COVID-19) continues to be a major public health challenge globally. The identification of SARS-CoV-2-derived T cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19.METHODSIn this study, a number of SARS-CoV-2-derived HLA-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using PBMCs from unexposed individuals (negative for SARS-CoV-2 IgG).RESULTSSeven epitopes derived from 4 SARS-CoV-2 proteins were identified. Interestingly, most (5 out of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations.CONCLUSIONSIn summary, in the current study, we present an alternative and effective strategy for the identification of T cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.