scholarly journals SARS -CoV-2 T-cell immunity to variants of concern following vaccination

2021 ◽  
Author(s):  
Kathleen M.E. Gallagher ◽  
Mark B. Leick ◽  
Rebecca C. Larson ◽  
Trisha R. Berger ◽  
Katelin Katsis ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Entry ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Host Cells ◽  
Viral Control ◽  
Cell Responses ◽  
Cell Immunity

Recently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence. A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein, which is required for viral entry to host cells. Immunity to SARS-CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants, investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants.

scholarly journals Induction of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses in HIV Vaccine Trial Participants Who Subsequently Acquire HIV-1 Infection

2006 ◽  
Vol 80 (19) ◽  
pp. 9779-9788 ◽  
Author(s):  
Helen Horton ◽  
Colin Havenar-Daughton ◽  
Deborah Lee ◽  
Erin Moore ◽  
Jianhong Cao ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1

ABSTRACT Candidate human immunodeficiency virus type 1 (HIV-1) vaccines designed to elicit T-cell immunity in HIV-1-uninfected persons are under investigation in phase I to III clinical trials. Little is known about how these vaccines impact the immunologic response postinfection in persons who break through despite vaccination. Here, we describe the first comprehensive characterization of HIV-specific T-cell immunity in vaccine study participants following breakthrough HIV-1 infection in comparison to 16 nonvaccinated subjects with primary HIV-1 infection. Whereas none of the 16 breakthrough infections possessed vaccine-induced HIV-1-specific T-cell responses preinfection, 85% of vaccinees and 86% of nonvaccinees with primary HIV-1 infection developed HIV-specific T-cell responses postinfection. Breakthrough subjects' T cells recognized 43 unique HIV-1 T-cell epitopes, of which 8 are newly described, and 25% were present in the vaccine. The frequencies of gamma interferon (IFN-γ)-secreting cells recognizing epitopes within gene products that were and were not encoded by the vaccine were not different (P = 0.64), which suggests that responses were not anamnestic. Epitopes within Nef and Gag proteins were the most commonly recognized in both vaccinated and nonvaccinated infected subjects. One individual controlled viral replication without antiretroviral therapy and, notably, mounted a novel HIV-specific HLA-C14-restricted Gag LYNTVATL-specific T-cell response. Longitudinally, HIV-specific T cells in this individual were able to secrete IFN-γ and tumor necrosis factor alpha, as well as proliferate and degranulate in response to their cognate antigenic peptides up to 5 years postinfection. In conclusion, a vaccinee's ability to mount an HIV-specific T-cell response postinfection is not compromised by previous immunization, since the CD8+ T-cell responses postinfection are similar to those seen in vaccine-naïve individuals. Finding an individual who is controlling infection highlights the importance of comprehensive studies of breakthrough infections in vaccine trials to determine whether host genetics/immune responses and/or viral characteristics are responsible for controlling viral replication.

scholarly journals Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

2017 ◽  
Vol 91 (24) ◽  
Author(s):  
Alba Grifoni ◽  
John Pham ◽  
John Sidney ◽  
Patrick H. O'Rourke ◽  
Sinu Paul ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Zika Virus ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACT While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins. IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.

scholarly journals Phase I Trial of a Multi-Peptide COVID-19 Vaccine for the Induction of SARS-CoV-2 T-Cell Immunity

2021 ◽  
Author(s):  
Juliane Walz ◽  
Jonas Heitmann ◽  
Tatjana Bilich ◽  
Claudia Tandler ◽  
Annika Nelde ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Phase I ◽  
T Cell Responses ◽  
T Cell Response ◽  
T Cell Immunity ◽  
T Cell Epitopes ◽  
Serious Adverse Events ◽  
Cell Responses ◽  
Cell Immunity

Abstract T-cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T-cell epitopes derived from various viral proteins, combined with the toll-like receptor 1/2 agonist XS15 emulsified in MontanideTM ISA51 VG, aiming to induce superior SARS-CoV-2 T-cell immunity to combat COVID-19. We conducted a Phase I open-label trial, including 36 participants aged 18 to 80 years, who received one single subcutaneous CoVAC-1 vaccination. The primary endpoint was safety analyzed until day 56. Immunogenicity in terms of CoVac-1-induced T-cell response was analyzed as main secondary endpoint until day 28. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study subjects, while systemic reactogenicity was absent or mild. SARS-CoV-2-specific T-cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T-helper 1 CD4+ and CD8+ T cells. CoVac-1-induced interferon-γ T-cell responses by far surpassed those detected in COVID-19 convalescents and were unaffected by current SARS-CoV-2 variants of concern (VOC). Together, CoVac-1 showed a favorable safety profile and induced broad, potent, and VOC-independent T-cell responses, supporting the presently ongoing evaluation in a Phase II trial for patients with B-cell/antibody deficiency. Funded by the Ministry of Science, Research and the Arts Baden-Württemberg, Germany; ClinicalTrials.gov number, NCT04546841.

scholarly journals SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron

2021 ◽  
Author(s):  
Roanne Keeton ◽  
Marius B Tincho ◽  
Amkele Ngomti ◽  
Richard Baguma ◽  
Ntombi Benede ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
T Cell Responses ◽  
Study Groups ◽  
T Cell Response ◽  
Cell Responses ◽  
Cell Immunity

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. 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. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% 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 to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

scholarly journals Mucosal vaccination induces protection against SARS-CoV-2 in the absence of detectable neutralizing antibodies

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chaojie Zhong ◽  
Hongjie Xia ◽  
Awadalkareem Adam ◽  
Binbin Wang ◽  
Renee L. Hajnik ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Lung Inflammation ◽  
Neutralizing Antibodies ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Viral Loads ◽  
Mucosal Vaccination ◽  
Cell Responses ◽  
Cell Immunity

AbstractA candidate multigenic SARS-CoV-2 vaccine based on an MVA vector expressing both viral N and S proteins (MVA-S + N) was immunogenic, and induced T-cell responses and binding antibodies to both antigens but in the absence of detectable neutralizing antibodies. Intranasal immunization with the vaccine diminished viral loads and lung inflammation in mice after SARS-CoV-2 challenge, which correlated with the T-cell response induced by the vaccine in the lung, indicating that T-cell immunity is also likely critical for protection against SARS-CoV-2 infection in addition to neutralizing antibodies.

538 Harnessing cross-dressing dendritic cells to strengthen anti-tumor immunity

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A574-A574
Author(s):  
Ellen Duong ◽  
Timothy Fessenden ◽  
Arjun Bhutkar ◽  
Stefani Spranger
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cancer Cell ◽  
Tumor Immunity ◽  
T Cell Responses ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity ◽  
Cross Dressing

BackgroundCytotoxic (CD8+) T-cells are required for tumor eradication and durable anti-tumor immunity.1 The induction of tumor-reactive CD8+ T-cells is predominately attributed to a subset of dendritic cells (DC) called Batf3-driven DC1, given their robust ability to cross-present antigens for T-cell priming and their role in effector T-cell recruitment.2–4 Presence of the DC1 signature in tumors correlates with improved survival and response to immunotherapies.5–7 Yet, most tumors with a DC1 infiltrate still progress, suggesting that while DC1 can initiate tumor-reactive CD8+ T-cell responses, they are unable to sustain them. Therefore, there is a critical need to identify and engage additional stimulatory DC subsets to strengthen anti-tumor immunity and boost immunotherapy responses.MethodsTo identify DC subsets that drive poly-functional CD8+ T-cell responses, we compared the DC infiltrate of a spontaneously regressing tumor with a progressing tumor. Multicolor flow immunophenotyping and single-cell RNA-sequencing were used to profile the DC compartment of both tumors. IFNγ-ELISpot was performed on splenocytes to assess for systemic tumor-reactive T-cell responses. Sorted DC subsets from tumors were co-cultured with TCR-transgenic T-cells ex vivo to evaluate their stimulatory capacity. Cross-dressing (in vivo/ex vivo) was assayed by staining for transfer of tumor-derived H-2b MHC complexes to Balb/c DC, which express the H-2d haplotype. Protective systemic immunity was assayed via contralateral flank tumor outgrowth experiments.ResultsRegressor tumors were infiltrated with more cross-presenting DC1 than progressor tumors. However, tumor-reactive CD8+ T-cell responses and tumor control were preserved in Batf3-/- mice lacking DC1, indicating that anti-tumor immune responses could be induced independent of DC1. Through functional assays, we established that anti-tumor immunity against regressor tumors required CD11c+ DC and cGAS/STING-independent type-I-interferon-sensing. Single-cell RNA-sequencing of the immune infiltrate of regressor tumors revealed a novel CD11b+ DC subset expressing an interferon-stimulated gene signature (ISG+ DC). Flow studies demonstrated that ISG+ DC were more enriched in regressor tumors than progressor tumors. We showed that ISG+ DC could activate CD8+ T-cells by cross-dressing with tumor-derived peptide-MHC complexes, thereby bypassing the requirement for cross-presentation to initiate CD8+ T-cell-driven immunity. ISG+ DC highly expressed cytosolic dsRNA sensors (RIG-I/MDA5) and could be therapeutically harnessed by exogenous addition of a dsRNA analog to drive protective CD8+ T-cell responses in DC1-deficient mice.ConclusionsThe DC infiltrate in tumors can dictate the strength of anti-tumor immunity. Harnessing multiple stimulatory DC subsets, such as cross-presenting DC1 and cross-dressing ISG+ DC, provides a therapeutic opportunity to enhance anti-tumor immunity and increase immunotherapy responses.ReferencesFridman WH, et al. The immune contexture in human tumours: impact on clinical outcome. Nature Reviews Cancer 2012;12(4): p. 298–306.Hildner K, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 2008;322(5904):p. 1097–100.Spranger S, et al. Tumor-Residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 2017;31(5):p. 711–723.e4.Roberts, EW, et al., Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell 2016;30(2): p. 324–336.Broz ML, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 2014;26(5): p. 638–52.Salmon H., et al., Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity, 2016. 44(4): p. 924–38.Sánchez-Paulete AR, et al., Cancer immunotherapy with immunomodulatory anti-CD137 and Anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov, 2016;6(1):p. 71–9.

scholarly journals Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322924
Author(s):  
Tuxiong Huang ◽  
Xiang-Yu Tan ◽  
Hui-Si Huang ◽  
Yu-Ting Li ◽  
Bei-Lei Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
Tumour Microenvironment ◽  
T Cell Response ◽  
Cell Responses ◽  
Cancer Associated Fibroblast ◽  
Anticancer Immunotherapy ◽  
Novel Therapeutic Strategies

ObjectiveSolid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC).DesignAnti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses.ResultsA negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades.ConclusionsCAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.

scholarly journals Role of Thymic Output in Regulating CD8 T-Cell Homeostasis during Acute and Chronic Viral Infection

2005 ◽  
Vol 79 (15) ◽  
pp. 9419-9429 ◽  
Author(s):  
Nicole E. Miller ◽  
Jennifer R. Bonczyk ◽  
Yumi Nakayama ◽  
M. Suresh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Lcmv Infection

ABSTRACT Although it is well documented that CD8 T cells play a critical role in controlling chronic viral infections, the mechanisms underlying the regulation of CD8 T-cell responses are not well understood. Using the mouse model of an acute and chronic lymphocytic choriomeningitis virus (LCMV) infection, we have examined the relative importance of peripheral T cells and thymic emigrants in the elicitation and maintenance of CD8 T-cell responses. Virus-specific CD8 T-cell responses were compared between mice that were either sham thymectomized or thymectomized (Thx) at ∼6 weeks of age. In an acute LCMV infection, thymic deficiency did not affect either the primary expansion of CD8 T cells or the proliferative renewal and maintenance of virus-specific lymphoid and nonlymphoid memory CD8 T cells. Following a chronic LCMV infection, in Thx mice, although the initial expansion of CD8 T cells was normal, the contraction phase of the CD8 T-cell response was exaggerated, which led to a transient but striking CD8 T-cell deficit on day 30 postinfection. However, the virus-specific CD8 T-cell response in Thx mice rebounded quickly and was maintained at normal levels thereafter, which indicated that the peripheral T-cell repertoire is quite robust and capable of sustaining an effective CD8 T-cell response in the absence of thymic output during a chronic LCMV infection. Taken together, these findings should further our understanding of the regulation of CD8 T-cell homeostasis in acute and chronic viral infections and might have implications in the development of immunotherapy.

scholarly journals Listeria Monocytogenes: A Model Pathogen Continues to Refine Our Knowledge of the CD8 T Cell Response

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 55 ◽  
Author(s):  
Zhijuan Qiu ◽  
Camille Khairallah ◽  
Brian Sheridan
Keyword(s):  
Listeria Monocytogenes ◽  
T Cell ◽  
Cell Response ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Oral Infection ◽  
T Cell Response ◽  
Infection Model ◽  
Cell Responses

Listeria monocytogenes (Lm) infection induces robust CD8 T cell responses, which play a critical role in resolving Lm during primary infection and provide protective immunity to re-infections. Comprehensive studies have been conducted to delineate the CD8 T cell response after Lm infection. In this review, the generation of the CD8 T cell response to Lm infection will be discussed. The role of dendritic cell subsets in acquiring and presenting Lm antigens to CD8 T cells and the events that occur during T cell priming and activation will be addressed. CD8 T cell expansion, differentiation and contraction as well as the signals that regulate these processes during Lm infection will be explored. Finally, the formation of memory CD8 T cell subsets in the circulation and in the intestine will be analyzed. Recently, the study of CD8 T cell responses to Lm infection has begun to shift focus from the intravenous infection model to a natural oral infection model as the humanized mouse and murinized Lm have become readily available. Recent findings in the generation of CD8 T cell responses to oral infection using murinized Lm will be explored throughout the review. Finally, CD8 T cell-mediated protective immunity against Lm infection and the use of Lm as a vaccine vector for cancer immunotherapy will be highlighted. Overall, this review will provide detailed knowledge on the biology of CD8 T cell responses after Lm infection that may shed light on improving rational vaccine design.

scholarly journals Public T-cell epitopes shared among SARS-CoV-2 variants are presented on prevalent HLA class I alleles

2021 ◽  
Author(s):  
Saskia Meyer ◽  
Isaac Blaas ◽  
Ravi Chand Bollineni ◽  
Marina Delic-Sarac ◽  
Trung T Tran ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
Hla Class I ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Class I ◽  
T Cell Epitopes ◽  
Low Frequencies ◽  
Cell Responses

T-cell epitopes with broad population coverage may form the basis for a new generation of SARS-CoV-2 vaccines. However, published studies on immunoprevalence are limited by small test cohorts, low frequencies of antigen-specific cells and lack of data correlating eluted HLA ligands with T-cell responsiveness. Here, we investigate CD8 T-cell responses to 48 peptides eluted from prevalent HLA alleles, and an additional 84 predicted binders, in a large cohort of convalescents (n=83) and pre-pandemic control samples (n=19). We identify nine conserved SARS-CoV-2 specific epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians, to which responding CD8 T cells are detected in 70-100% of convalescents expressing the relevant HLA allele, including two novel epitopes. We find a strong correlation between immunoprevalence and immunodominance. Using a new algorithm, we predict that a vaccine including these epitopes would induce a T cell response in 83% of Caucasians. Significance Statement: Vaccines that induce broad T-cell responses may boost immunity as protection from current vaccines against SARS-CoV-2 is waning. From a manufacturing standpoint, and to deliver the highest possible dose of the most immunogenic antigens, it is rational to limit the number of epitopes to those inducing the strongest immune responses in the highest proportion of individuals in a population. Our data show that the CD8 T cell response to SARS-CoV-2 is more focused than previously believed. We identify nine conserved SARS-CoV-2 specific CD8 T cell epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians and demonstrate that seven of these are endogenously presented.

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