SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors.

Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion or activation of preexisting immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4+ and CD8+ T cell responses to the spike protein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.

Viral T-cell epitopes - Identification, characterization and clinical application.

T-cell immunity, mediated by CD4+ and CD8+ T cells, represents a cornerstone in the control of viral infections. Virus-derived T-cell epitopes are represented by human leukocyte antigen (HLA)-presented viral peptides on the surface of virus-infected cells. They are the prerequisite for the recognition of infected cells by T cells. Knowledge of viral T-cell epitopes provides on the one hand a diagnostic tool to decipher protective T-cell immune responses in the human population and on the other hand various prophylactic and therapeutic options including vaccination approaches and the transfer of virus-specific T cells. Such approaches have already been proven to be effective against various viral infections, particularly in immunocompromised patients lacking sufficient humoral, antibody-based immune response. This review provides an overview on the state of the art as well as current studies regarding the identification and characterization of viral T-cell epitopes and approaches of clinical application. In the first chapter in silico prediction tools and direct, mass spectrometry-based identification of viral T-cell epitopes is compared. The second chapter provides an overview of commonly used assays for further characterization of T-cell responses and phenotypes. The final chapter presents an overview of clinical application of viral T-cell epitopes with a focus on human immunodeficiency virus (HIV), human cytomegalovirus (HCMV) and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), being representatives of relevant viruses.

Not all T cell epitopes are equally desired: a review of in silico tools for the prediction of cytokine-inducing potential of T-cell epitopes.

Assessment of protective or harmful T cell response induced by any antigenic epitope is important in designing any immunotherapeutic molecule. The understanding of cytokine induction potential also helps us to monitor antigen-specific cellular immune responses and rational vaccine design. The classical immunoinformatics tools served well for prediction of B cell and T cell epitopes. However, in the last decade, the prediction algorithms for T cell epitope inducing specific cytokines have also been developed and appreciated in the scientific community. This review summarizes the current status of such tools, their applications, background algorithms, their use in experimental setup and functionalities available in the tools/web servers.

Routine evaluation of HBV-specific T cell reactivity in chronic hepatitis B using a broad-spectrum T-cell epitope peptide library and ELISpot assay.

BACKGROUND: The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. METHODS: A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3-5 months. RESULTS: The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = - 0.21, - 0.21, - 0.27, - 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. CONCLUSION: The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.

Epitope prediction and identification- adaptive T cell responses in humans.

Epitopes, in the context of T cell recognition, are short peptides typically derived by antigen processing, and presented on the cell surface bound to MHC molecules (HLA molecules in humans) for TCR scrutiny. The identification of epitopes is a context-dependent process, with consideration given to, for example, the source pathogen and protein, the host organism, and state of the immune reaction (e.g., following natural infection, vaccination, etc.). In the following review, we consider the various approaches used to define T cell epitopes, including both bioinformatic and experimental approaches, and discuss the concepts of immunodominance and immunoprevalence. We also discuss HLA polymorphism and epitope restriction, and the resulting impact on the identification of, and potential population coverage afforded by, epitopes or epitope-based vaccines. Finally, some examples of the practical application of T cell epitope identification are provided, showing how epitopes have been valuable for deriving novel immunological insights in the context of the immune response to various pathogens and allergens.

Identification of cow milk epitopes to characterize and quantify disease-specific T cells in allergic children.

BACKGROUND: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food challenges). OBJECTIVE: We sought to determine whether allergen-specific T cells in CM-allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. METHODS: Using PBMCs from 147 food-allergic pediatric subjects, we mapped T-cell responses to a set of reactive epitopes in CM that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing subjects with CMA from subjects without CMA. We further used the pool to isolate and characterize antigen-specific CD4 memory T cells using flow cytometry and single-cell RNA/TCR sequencing assays. RESULTS: We detected significant changes in the transcriptional program and clonality of CM antigen-specific (CM+) T cells elicited by the pool in subjects with CMA versus subjects without CMA ex vivo. CM+ T cells from subjects with CMA had increased percentages of FOXP3+ cells over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells that have suppressive activity, but CM+ FOXP3+ cells from subjects with CMA showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared with subjects without CMA, suggesting that these are not conventional regulatory T cells. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to use surface markers (CD25, CD127, and CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow-cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from subjects with CMA in an independent cohort, which could be used for diagnostic purposes. Looking specifically for TH2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in subjects with CMA and that had high expression of TH2 cytokines and pathogenic TH2/T follicular helper markers. CONCLUSIONS: Overall, these findings suggest that there are several differences in the phenotypes of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.

Experimental Data on PIRCHE and T-Cell Reactivity: HLA-DPB1-Derived Peptides Identified by PIRCHE-I Show Binding to HLA-A*02:01 in vitro and T-Cell Activation in vivo.

Introduction: Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8+ T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo. Methods: PIRCHE-I analysis was performed to identify HLA-DPB1-derived peptides that could theoretically bind to HLA-A*02:01. PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro by investigating binding affinities of HLA-DPB1-derived peptides to the HLA-A*02:01 in a competition-based binding assay. To investigate the capacity of HLA-DPB1-derived peptides to elicit a T-cell response in vivo, mice were immunized with these peptides. T-cell alloreactivity was subsequently evaluated using an interferon-gamma ELISpot assay. Results: The PIRCHE-I algorithm identified five HLA-DPB1-derived peptides (RMCRHNYEL, YIYNREEFV, YIYNREELV, YIYNREEYA, and YIYNRQEYA) to be presented by HLA-A*02:01. Binding of these peptides to HLA-A*02:01 was confirmed in a competition-based peptide binding assay, all showing an IC50 value of 21 µm or lower. The peptides elicited an interferon-gamma response in vivo. Conclusion: Our results indicate that the PIRCHE-I algorithm can identify potential immunogenic HLA-DPB1-derived peptides present in recipients of an HLA-DPB1-mismatched donor. These combined in vitro and in vivo observations strengthen the validity of the PIRCHE-I algorithm to identify HLA-DPB1 mismatch-related GvHD development upon HSCT.

Utilizing the Banana S-Adenosyl-L-Homocysteine Hydrolase Allergen to Identify Cross-Reactive IgE in Ryegrass-, Latex-, and Kiwifruit-Allergic Individuals.

Food allergies mediated by specific IgE (sIgE) have a significant socioeconomic impact on society. Evaluating the IgE cross-reactivity between allergens from different allergen sources can enable the better management of these potentially life-threatening adverse reactions to food proteins and enhance food safety. A novel banana fruit allergen, S-adenosyl-L-homocysteine hydrolase (SAHH), has been recently identified and its recombinant homolog was heterologously overproduced in E. coli. In this study, we performed a search in the NCBI (National Center for Biotechnology Information) for SAHH homologs in ryegrass, latex, and kiwifruit, all of which are commonly associated with pollen-latex-fruit syndrome. In addition, Western immunoblot analysis was utilized to identify the cross-reactive IgE to banana SAHH in the sera of patients with a latex allergy, kiwifruit allergy, and ryegrass allergy. ClustalOmega analysis showed more than 92% amino acid sequence identity among the banana SAHH homologs in ryegrass, latex, and kiwifruit. In addition to five B-cell epitopes, in silico analysis predicted eleven T-cell epitopes in banana SAHH, seventeen in kiwifruit SAHH, twelve in ryegrass SAHH, and eight in latex SAHH, which were related to the seven-allele HLA reference set (HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01, HLA-DRB5*01:01). Four T-cell epitopes were identical in banana and kiwifruit SAHH (positions 328, 278, 142, 341), as well as banana and ryegrass SAHH (positions 278, 142, 96, and 341). All four SAHHs shared two T-cell epitopes (positions 278 and 341). In line with the high amino acid sequence identity and B-cell epitope homology among the analyzed proteins, the cross-reactive IgE to banana SAHH was detected in three of three latex-allergic patients, five of six ryegrass-allergic patients, and two of three kiwifruit-allergic patients. Although banana SAHH has only been studied in a small group of allergic individuals, it is a novel cross-reactive food allergen that should be considered when testing for pollen-latex-fruit syndrome.

PEPMatch: a tool to identify short peptide sequence matches in large sets of proteins.

BACKGROUND: Numerous tools exist for biological sequence comparisons and search. One case of particular interest for immunologists is finding matches for linear peptide T cell epitopes, typically between 8 and 15 residues in length, in a large set of protein sequences. Both to find exact matches or matches that account for residue substitutions. The utility of such tools is critical in applications ranging from identifying conservation across viral epitopes, identifying putative epitope targets for allergens, and finding matches for cancer-associated neoepitopes to examine the role of tolerance in tumor recognition. RESULTS: We defined a set of benchmarks that reflect the different practical applications of short peptide sequence matching. We evaluated a suite of existing methods for speed and recall and developed a new tool, PEPMatch. The tool uses a deterministic k-mer mapping algorithm that preprocesses proteomes before searching, achieving a 50-fold increase in speed over methods such as the Basic Local Alignment Search Tool (BLAST) without compromising recall. PEPMatch's code and benchmark datasets are publicly available. CONCLUSIONS: PEPMatch offers significant speed and recall advantages for peptide sequence matching. While it is of immediate utility for immunologists, the developed benchmarking framework also provides a standard against which future tools can be evaluated for improvements. The tool is available at https://nextgen-tools.iedb.org , and the source code can be found at https://github.com/IEDB/PEPMatch .

Evolution of SARS-CoV-2-specific CD4+ T cell epitopes.

Vaccination clearly decreases coronavirus disease 2019 (COVID-19) mortality; however, they also impose selection pressure on the virus, which promotes the evolution of immune escape variants. For example, despite the high vaccination level in especially Western countries, the Omicron variant caused millions of breakthrough infections, suggesting that the highly mutated spike protein in the Omicron variant can escape antibody immunity much more efficiently than the other variants of concern (VOCs). In this study, we investigated the resistance/susceptibility of T helper cell responses that are necessary for generating efficient long-lasting antibody immunity, in several VOCs. By predicting T helper cell epitopes on the spike protein for most common HLA-DRB1 alleles worldwide, we found that although most of high frequency HLA-DRB1 alleles have several potential T helper cell epitopes, few alleles like HLA-DRB1 13:01 and 11:01 are not predicted to have any significant T helper cell responses after vaccination. Using these predictions, a population based on realistic human leukocyte antigen-II (HLA-II) frequencies were simulated to visualize the T helper cell immunity on the population level. While a small fraction of this population had alarmingly little predicted CD4 T cell epitopes, the majority had several epitopes that should be enough to generate efficient B cell responses. Moreover, we show that VOC spike mutations hardly affect T helper epitopes and mainly occur in other residues of the spike protein. These results suggest that lack of long-lasting antibody responses is not likely due to loss of T helper cell epitopes in new VOCs.

Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine.

Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.

Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase.

Citrullinated proteins and anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). It has been suggested that during inflammation or dysbiosis, bacteria could initiate production of ACPAs. Most patients with RA are seropositive for ACPAs, but these antibodies have overlapping reactivity to different posttranslational modifications (PTMs). For initiation and development of RA, T lymphocytes and T cell epitopes are still required. In this study, we evaluated the ability of bacterial L-asparaginase to modify RA-related T cell epitopes within type II collagen (CII259-273 and CII311-325), as well as whether these modified epitopes are recognized by ACPAs from RA patients. We included 12 patients with early RA and 11 healthy subjects selected according to predefined specific criteria. LC-MS/MS analyses revealed that the bacterial L-asparaginase can modify investigated T cell epitopes. ELISA tests showed cross-reactivity of ACPA positive sera from early RA patients towards the enzymatically modified immunodominant T cell epitopes within type II collagen (CII), but not to the modified irrelevant peptides. These data suggest that the cross-reactive ACPAs recognize the "carbonyl-Gly-Pro" motif in CII. Moreover, the T cell recognition of the modified major immunodominant T cell epitope Gal264-CII259-273 was not affected. This epitope was still able to activate autoreactive T cells from early RA patients. It is likely that such modifications are the missing link between the T cell priming and the development of anti-modified protein antibodies (AMPAs). Our results provide additional information on the etiology and pathogenesis of RA.

Tumour-associated antigenic peptides are present in the HLA class I ligandome of cancer cell line derived extracellular vesicles.

The recent success of monoclonal antibody checkpoint inhibitor therapies that enhance the ability of CD8+ T cells to detect cancer-related antigenic peptides has refocused the need to fully understand the repertoire of peptides being presented to the immune system. Whilst the peptide ligandome presented by cell surface human leucocyte antigen class I (HLA-I) molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles (EVs) remains poorly defined. Here, we report the HLA-I ligandome of both the cell surface and EVs from eight breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-361, MDA-MB-415, MDA-MB-453, HCC 1806, HCC 1395, and HCC 1954), and additionally the melanoma cell line ESTDAB-056 and the multiple myeloma line RPMI 8226. Utilizing HLA-I immunoisolation and mass spectrometry, we detected a total of 6574 peptides from the cell surface and 2461 peptides from the EVs of the cell lines studied. Within the EV HLA-I ligandome, we identified 150 peptides derived from tumour associated antigenic proteins, of which 19 peptides have been shown to elicit T-cell responses in previous studies. Our data thus show the prevalence of clinically relevant tumour-associated antigenic peptides in the HLA-I ligandome presented on EV.

Immune epitopes identification and designing of a multi-epitope vaccine against bovine leukemia virus: a molecular dynamics and immune simulation approaches.

BACKGROUND: Bovine leukemia virus (BLV) is an oncogenic delta-retrovirus causing bovine leucosis. Studies on BLV have shown the association with human breast cancer. However, the exact molecular mechanism is neither known nor their appropriate preventative measure to halt the disease initiation and progression. In this study, we designed a multi-epitope vaccine against BLV using a computational analyses. METHODS: Following a rigorous assessment, the vaccine was constructed using the T-cell epitopes from each BLV-derived protein with suitable adjuvant and linkers. Both physicochemistry and immunogenic potency as well as the safeness of the vaccine candidate were assessed. Population coverage was done to evaluate the vaccine probable efficiency in eliciting the immune response worldwide. After homology modeling, the three-dimensional structure was refined and validated to determine the quality of the designed vaccine. The vaccine protein was then subjected to molecular docking with Toll-like receptor 3 (TLR3) to evaluate the binding efficiency followed by dynamic simulation for stable interaction. RESULTS: Our vaccine construct has the potential immune response and good physicochemical properties. The vaccine is antigenic and immunogenic, and has no allergenic or toxic effect on the human body. This novel vaccine contains a significant interactions and binding affinity with the TLR3 receptor. CONCLUSIONS: The proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat BLV infections. However, experimental evaluations are essential to validate the exact safety and immunogenic profiling of this vaccine.

Per a 5-derived T-cell peptides modulate NF-kB signalling to ameliorate allergic inflammation systemically in murine model of cockroach allergic hyper-reactivity.

Peptide immunotherapy (PIT) represents a safe and efficacious therapeutic regimen with in-consequential side-effects. The present study aims to identify T-cell epitopes of Per a 5 allergen, a delta class GST from Periplaneta americana and investigate effect of peptide treatment in murine model of cockroach allergen-mediated hyper-reactivity. The epitopes (TC-P1, TC-P2, and TC-P3) were identified as promiscuous MHC-II binders by MHC-Pred, ProPred, and IEDB analysis tool. Murine model of cockroach allergic hyper-reactivity was generated in Balb/c mice. A marked reduction in cellular infiltration in lungs (3-fold compared with Non-IT) was observed in T3-IT group as evidenced by total leucocyte count in BALF and histology. Specific IgE levels were reduced 3-fold in T2-IT and T3-IT compared with Non-IT with increase in IgG2a levels. IL-4 and IL-13 were reduced upto 2.5-fold in treatment groups compared with Non-IT group. Splenocytes revealed significant increase in levels of CD4+FoxP3+ T cells in TC-P1 and TC-P2 mice demonstrating a systemic shift towards Tregs. Peptide treatment downregulated NF-kB signalling in lung and enhanced the levels of immune-regulatory molecules α1-antitrypsin and elafin. Our results indicate that TC-P1 and TC-P3 alter Th2 cytokine milieu and antibody isotype ratio to suppress allergic inflammation. PIT modulates local and systemic mechanisms to resolve inflammation and possess potential for treatment in cockroach allergy.

The interdependence of machine learning and LC-MS approaches for an unbiased understanding of the cellular immunopeptidome.

INTRODUCTION: The comprehensive collection of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface is collectively known as the immunopeptidome. The analysis and interpretation of such data sets holds great promise for furthering our understanding of basic immunology and adaptive immune activation and regulation, and for direct rational discovery of T cell antigens and the design of T-cell-based therapeutics and vaccines. These applications are, however, challenged by the complex nature of immunopeptidome data. AREAS COVERED: Here, we describe the benefits and shortcomings of applying liquid chromatography-tandem mass spectrometry (MS) to obtain large-scale immunopeptidome data sets and illustrate how the accurate analysis and optimal interpretation of such data is reliant on the availability of refined and highly optimized machine learning approaches. EXPERT OPINION: Further, we demonstrate how the accuracy of immunoinformatics prediction methods within the field of MHC antigen presentation has benefited greatly from the availability of MS-immunopeptidomics data, and exemplify how optimal antigen discovery is best performed in a synergistic combination of MS experiments and such in silico models trained on large-scale immunopeptidomics data.

A comprehensive study of epitopes and immune reactivity among Plasmodium species.

BACKGROUND: Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays. METHODS: Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively. RESULTS: The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10. CONCLUSIONS: This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response.

Identification of promising CD8 and CD4 T cell epitopes for peptide vaccine formulation against SARS-CoV-2.

The novel virus "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" has been responsible for the worldwide pandemic causing huge devastation and deaths since December 2019. The disease caused by this virus is known as COVID-19. The present study is based on immuno-informatics approach to develop a multi-epitope-loaded peptide vaccine to combat the COVID-19 menace. Here, we have reported the 9-mer CD8 T cell epitopes and 15-mer CD4 T cell epitopes, free from glycosylation sites, belonging to three proteins, viz. surface glycoprotein, membrane glycoprotein and envelope protein of this virus. Immunogenicity, aliphatic amino acid, antigenicity and hydrophilicity scores of the predicted epitopes were estimated. In addition, other physicochemical parameters, namely net charge, Boman index and amino acid contents, were also accounted. Out of all the epitopes, three CD8 T cell epitopes viz. PDPSKPSKR, DPSKPSKRS and QTQTNSPRR and three CD4 T cell epitopes viz. ASYQTQTNSPRRARS, RIGNYKLNTDHSSSS and RYRIGNYKLNTDHSS were found to be efficient targets for raising immunity in human against this virus. With the help of our identified potent epitopes, various pharma industries might initiate efforts to incorporate those epitopes with carrier protein or adjuvant to develop a multi-epitope-loaded peptide vaccine against SARS-CoV-2. The peptide vaccines are usually cost-effective and therefore, could be administered as a preventive measure to combat the spread of this disease. Proper clinical trials must be conducted prior to the use of identified epitopes as vaccine candidates.

Will Peptides Help to Stop COVID-19?

Peptides are widely used for the diagnostics, prevention, and therapy of certain human diseases. How useful can they be for the disease caused by the SARS-CoV-2 coronavirus? In this review, we discuss the possibility of using synthetic and recombinant peptides and polypeptides for prevention of COVID-19 via blocking the interaction between the virus and its main receptor ACE2, as well as components of antiviral vaccines, in particular, against new emerging virus variants.

Modification of Regulatory T Cell Epitopes Promotes Effector T Cell Responses to Aspartyl/Asparaginyl ß-Hydroxylase.

Cancer is a leading cause of death worldwide. The search for innovative therapeutic approaches is a principal focus of medical research. Vaccine strategies targeting a number of tumor-associated antigens are currently being evaluated. To date, none have garnered significant success. Purportedly, an immunosuppressive tumor microenvironment and the accumulation of regulatory T cells contribute to a lack of tumor vaccine efficacy. Aspartyl/asparaginyl ß-hydroxylase (ASPH), a promising therapeutic target, is overexpressed in a variety of malignant tumors but is expressed negligibly in normal tissues. Computer analysis predicted that ASPH expresses four peptide sequences (epitopes) capable of stimulating regulatory T cell activity. The abolition of these putative regulatory T cell epitopes increased the CD4+ and CD8+ effector T cell responses to monocyte-derived dendritic cells pulsed with a modified, epitope-depleted version of ASPH in an ex vivo human lymphoid tissue-equivalent coculture system while simultaneously decreasing the overall number of FoxP3+ regulatory T cells. These findings suggest that the efficacy of all new vaccine candidates would profit from screening and eliminating potential tolerogenic regulatory T cell epitopes.