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2.
Int Immunopharmacol ; 112: 109283, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2105145

ABSTRACT

BACKGROUND: Coronavirus 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. METHODS: In 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. RESULTS: Combinations 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. CONCLUSIONS: The 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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/therapy , Epitopes , Receptors, Antigen, T-Cell/genetics , Antibodies, Monoclonal/therapeutic use , RNA-Dependent RNA Polymerase , Cytokines , Epitopes, T-Lymphocyte/genetics
3.
Immunity ; 55(11): 1993-2005, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2105131

ABSTRACT

The lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA platform has been used to generate safe and effective vaccines in record time against COVID-19. Here, we review the current understanding of the manner whereby mRNA vaccines induce innate immune activation and how this contributes to protective immunity. We discuss innate immune sensing of mRNA vaccines at the cellular and intracellular levels and consider the contribution of both the mRNA and the LNP components to their immunogenicity. A key message that is emerging from recent observations is that the LNP carrier acts as a powerful adjuvant for this novel vaccine platform. In this context, we highlight important gaps in understanding and discuss how new insight into the mechanisms underlying the effectiveness of mRNA-LNP vaccines may enable tailoring mRNA and carrier molecules to develop vaccines with greater effectiveness and milder adverse events in the future.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , Vaccines, Synthetic , RNA, Messenger/genetics , Immunity, Innate
4.
Infect Dis (Lond) ; : 1-7, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2107229

ABSTRACT

BACKGROUND: Vaccination against SARS-CoV-2 reduces the risk of hospitalisation and death, but vaccine-induced IgG antibodies against the spike protein (IgG S) decline over time. Less is known about the nature of the vaccine-induced T-cell response to SARS-CoV-2 antigens. METHODS: IgG antibodies against nucleocapsid protein (IgG N), IgG S, and T-cell response towards SARS-CoV-2 antigens were determined in samples taken between November 2020 and November 2021 from a cohort of healthcare workers at an Infectious Diseases Department. RT-PCR screening for SARS-CoV-2 was encouraged once every four weeks in addition to testing when symptomatic or identified through contact tracing. Vaccination data were collected at the end of the study. RESULTS: At inclusion, T-cell response to SARS-CoV-2 antigens was found in 10/15 (66.7%) of participants with a previous/current COVID-19 infection and in 9/54 (16.7%) of participants with no prior/current history of COVID-19 infection. All participants with complete follow-up (n = 59) received two doses of a SARS-CoV-2 vaccine during the study. All participants demonstrated detectable IgG (S) antibodies at the end of the study, in median 278 days (IQR 112) after the second vaccine dose. All but four participants displayed T-cell responses towards SARS-CoV-2 antigens. IgG S antibody levels correlated with time since the second vaccine dose. In addition, previous COVID-19 infection and the strength of the S1 T-cell response correlated with IgG S antibody levels. However, no correlation was demonstrated between the strength of the T-cell response and time since the second vaccine dose. CONCLUSION: COVID-19 vaccination induces robust T-cell responses that remain for at least nine months.

5.
Viruses ; 14(11)2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2099866

ABSTRACT

New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.


Subject(s)
Antiviral Agents , COVID-19 , Immune Evasion , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/virology , Mutation , Phylogeny , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics
6.
J Infect Dis ; 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2097373

ABSTRACT

Omicron variants are still the dominant SARS-CoV-2 viruses worldwide, therefore determining the level of protection from infection and severe disease is essential. Here, we investigated humoral and cellular immunity of individuals immunized by ChAdOx1, BNT162b2 and mRNA-1273 and our results show that IgG and neutralization titers wane over time. However, strongest neutralization against Omicron BA.1 and T cell responses were detected in ChAdOx1 vaccinees six months after the second dose, while no long lasting neutralization was shown against BA.2 in any cohort. Crucially, our investigation revealed that immunity against variants of concern is heterogenic and dependent on the immunization status.

7.
Int J Infect Dis ; 125: 195-208, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2095475

ABSTRACT

OBJECTIVES: To characterize the kinetics of humoral and T-cell responses in rheumatoid arthritis (RA)-patients followed up to 4-6 weeks (T3) after the SARS-CoV-2 vaccine booster dose. METHODS: Health care workers (HCWs, n = 38) and patients with RA (n = 52) completing the messenger RNA vaccination schedule were enrolled at T3. In each cohort, 25 subjects were sampled after 5 weeks (T1) and 6 months (T2) from the first vaccine dose. The humoral response was assessed by measuring anti-receptor-binding domain (RBD) and neutralizing antibodies, the T-cell response by interferon-γ-release assay (IGRA), T cell cytokine production, and B cell phenotype at T3 by flow cytometry. RESULTS: Patients with RA showed a significant reduction of antibody titers from T1 to T2 and a significant increase at T3. T-cell response by IGRA persisted over time in patients with RA, whereas it increased in HCWs. Most patients with RA scored positive for anti-RBD, neutralizing antibody and T-cell responses, although the magnitude was lower than HCWs. The spike-specific-cytokine response was mainly clusters of differentiation (CD)4+ T cells restricted in both cohorts and significantly lower with reduced interleukin-2 response and CD4-antigen-responding naïve T cells in patients with RA. Unswitched memory B cells were reduced in patients with RA compared with HCWs independently of vaccination. CONCLUSION: COVID-19 vaccine booster strengthens the humoral immunity in patients with RA even with a reduced cytokine response.

8.
Arch Med Res ; 53(7): 694-710, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2095059

ABSTRACT

BACKGROUND: The mutations in SARS-CoV-2 variants of concern (VOC) facilitate the virus' escape from the neutralizing antibodies induced by vaccines. However, the protection from hospitalization and death is not significantly diminished. Both vaccine boosters and infection improve immune responses and provide protection, suggesting that conserved and/or cross-reactive epitopes could be involved. While several important T- and B-cell epitopes have been identified, mainly in the S protein, the M and N proteins and their potential cross-reactive epitopes with other coronaviruses remain largely unexplored. AIMS: To identify and map new potential B- and T-cell epitopes within the SARS-CoV-2 S, M and N proteins, as well as cross-reactive epitopes with human coronaviruses. METHODS: Different bioinformatics tools were used to: i) Identify new and compile previously-reported B-and T-cell epitopes from SARS-CoV-2 S, M and N proteins; ii) Determine the mutations in S protein from VOC that affect B- and T-cell epitopes, and; iii) Identify cross-reactive epitopes with coronaviruses relevant to human health. RESULTS: New, potential B- and T-cell epitopes from S, M and N proteins as well as cross-reactive epitopes with other coronaviruses were found and mapped within the proteins' structures. CONCLUSION: Numerous potential B- and T-cell epitopes were found in S, M and N proteins, some of which are conserved between coronaviruses. VOCs present mutations within important epitopes in the S protein; however, a significant number of other epitopes remain unchanged. The epitopes identified here may contribute to augmenting the protective response to SARS-CoV-2 and its variants induced by infection and/or vaccination, and may also be used for the rational design of novel broad-spectrum coronavirus vaccines.


Subject(s)
COVID-19 , Epitopes, T-Lymphocyte , Humans , Epitopes, T-Lymphocyte/genetics , Computational Biology , SARS-CoV-2
9.
Front Bioinform ; 1: 622992, 2021.
Article in English | MEDLINE | ID: covidwho-2089804

ABSTRACT

Predictive models for vaccine design have become a powerful and necessary resource for the expeditiousness design of vaccines to combat the ongoing SARS-CoV-2 global pandemic. Here we use the power of these predicted models to assess the sequence diversity of circulating SARS-CoV-2 proteomes in the context of an individual's CD8 T-cell immune repertoire to identify potential. defined regions of immunogenicity. Using this approach of expedited and rational CD8 T-cell vaccine design, it may be possible to develop a therapeutic vaccine candidate with the potential for both global and local coverage.

10.
Scandinavian Journal of Immunology ; 2022.
Article in English | Web of Science | ID: covidwho-2088318

ABSTRACT

COVID-19, which emerged in December 2019 and continues to wreak havoc, has led to the death of many people around the world. In this study, we aimed to uncover the variables underlying the exacerbation of the disease by considering the changes in T cell subsets in adults and juveniles with different disease severity of COVID-19. Peripheral blood samples of 193 patients (128 adults and 65 juveniles) diagnosed with COVID-19 were evaluated in a flow cytometer, and a broad T cell profile was revealed by examining T cell subsets in terms of exhaustion and senescence. We found remarkable differences in the effector memory (EM;CD45RA(-)CCR7(-)) cell subsets of severe pneumonia cases. The frequencies of EM2 CD4(+) T, EM3 CD4(+) T, EM3 CD8(+) T, EM2 DN T and EM3 DN T cells were found to increase in severe pneumonia cases. Consistently, these cells were found in juveniles and uncomplicated adults in similar or lower proportions to healthy controls. The findings of our study provide a view of the T cell profile that may underlie differences in the course of COVID-19 cases in juveniles and adults and may provide new insights into the development of effective treatment strategies.

11.
Semin Immunol ; 61-64: 101661, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2086731

ABSTRACT

MAIT cells are one representative of a group of related unconventional or pre-set T cells, and are particularly abundant in humans. While these unconventional T cell types, which also include populations of Vδ2 cells and iNKT cells, recognise quite distinct ligands, they share functional features including the ability to sense "danger" by integration of cytokine signals. Since such signals are common to many human pathologies, activation of MAIT cells in particular has been widely observed. In this review we will discuss recent trends in these data, for example the findings from patients with Covid-19 and responses to novel vaccines. Covid-19 is an example where MAIT cell activation has been correlated with disease severity by several groups, and the pathways leading to activation are being clarified, but the overall role of the cells in vivo requires further exploration. Given the potential wide functional responsiveness of these cells, which ranges from tissue repair to cytotoxicity, and likely impacts on the activity of many other cell populations, defining the role of these cells - not only as sensitive biomarkers but also as mediators - across human disease remains an important task.

12.
J Med Virol ; : e28258, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2085072

ABSTRACT

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

13.
Clin Transl Immunology ; 11(10): e1421, 2022.
Article in English | MEDLINE | ID: covidwho-2085016

ABSTRACT

Objectives: Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Methods: Here, as a proof-of-concept, we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using the extracellular region of ACE2 and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus. Results: As in CAR-T cell approach, ACE2-Bite endowed cytotoxic cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type, and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins. Conclusion: In conclusion, these results suggest the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response.

14.
Clin Transl Immunology ; 11(10): e1422, 2022.
Article in English | MEDLINE | ID: covidwho-2084351

ABSTRACT

Objective: Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally, infecting humans and causing widespread morbidity and mortality. Here, we investigate the T cell response towards an immunodominant IAV epitope, NP265-273, and its IBV and ICV homologues, presented by HLA-A*03:01 molecule expressed in ~ 4% of the global population (~ 300 million people). Methods: We assessed the magnitude (tetramer staining) and quality of the CD8+ T cell response (intracellular cytokine staining) towards NP265-IAV and described the T cell receptor (TCR) repertoire used to recognise this immunodominant epitope. We next assessed the immunogenicity of NP265-IAV homologue peptides from IBV and ICV and the ability of CD8+ T cells to cross-react towards these homologous peptides. Furthermore, we determined the structures of NP265-IAV and NP323-IBV peptides in complex with HLA-A*03:01 by X-ray crystallography. Results: Our study provides a detailed characterisation of the CD8+ T cell response towards NP265-IAV and its IBV and ICV homologues. The data revealed a diverse repertoire for NP265-IAV that is associated with superior anti-viral protection. Evidence of cross-reactivity between the three different influenza virus strain-derived epitopes was observed, indicating the discovery of a potential vaccination target that is broad enough to cover all three influenza strains. Conclusion: We show that while there is a potential to cross-protect against distinct influenza virus lineages, the T cell response was stronger against the IAV peptide than IBV or ICV, which is an important consideration when choosing targets for future vaccine design.

15.
Virus Res ; 323: 198977, 2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2082653

ABSTRACT

Vaccines have been considered the most promising solution for ending the coronavirus disease 2019 (COVID-19) pandemic. Information regarding neutralizing antibodies (NAbs) and T-cell immune response in inactivated SARS-CoV-2 vaccine-immunized COVID-19 convalescent patients were either only available for a short time after illness recovered or not available at all (T-cell immunity). We evaluated SARS-CoV-2 NAbs and cellular immune responses to the SARS-CoV-2 inactivated vaccine in convalescent patients who recovered from infection for about one and a half years. We found that compared to before vaccination, SARS-CoV-2 NAbs and specific T-cell responses were significantly boosted by the inactivated vaccine in convalescent patients, which confirmed the pre-existing adaptive immunity in SARS-CoV-2 infected people. We observed that NAbs and IFN-γ-secreting T-cell response elicited by a single vaccine dose in subjects with prior COVID-19 infection were higher than after two doses of vaccine in SARS-CoV-2 naïve subjects. Both humoral and cellular immune responses elicited by one and two doses of inactivated vaccine were comparable in COVID-19-recovered persons. In conclusion, inactivated COVID-19 vaccine induced robust NAbs and T-cell responses to SARS-CoV-2 in COVID-19 convalescent patients and immune responses after one dose were equal to that after receiving two doses, which highlighted that robust humoral and cellular immune response can be reactivated by the inactivated vaccine in SARS-CoV-2 convalescent patients.

16.
Vaccine ; 40(48): 6963-6970, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2082524

ABSTRACT

BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection. METHODS: This is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot). FINDINGS: Two doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose. INTERPRETATION: CoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection.


Subject(s)
COVID-19 , Viral Vaccines , Humans , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Vaccines , Antibodies, Viral , Vaccination , Antibodies, Neutralizing , Immunoglobulin G/analysis , Th1 Cells , Vaccines, Inactivated
17.
Transplant Cell Ther ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2082370

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.

18.
Viruses ; 14(11)2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2081985

ABSTRACT

Reports on T-cell cross-reactivity against SARS-CoV-2 epitopes in unexposed individuals have been linked with prior exposure to the human common cold coronaviruses (HCCCs). Several studies suggested that cross-reactive T-cells response to live attenuated vaccines (LAVs) such as BCG (Bacillus Calmette-Guérin), OPV (Oral Polio Vaccine), and MMR (measles, mumps, and rubella) can limit the development and severity of COVID-19. This study aims to identify potential cross-reactivity between SARS-CoV-2, HCCCs, and LAVs in the context of T-cell epitopes peptides presented by HLA (Human Leukocyte Antigen) alleles of the Indonesian population. SARS-CoV-2 derived T-cell epitopes were predicted using immunoinformatics tools and assessed for their conservancy, variability, and population coverage. Two fully conserved epitopes with 100% similarity and nine heterologous epitopes with identical T-cell receptor (TCR) contact residues were identified from the ORF1ab fragment of SARS-CoV-2 and all HCCCs. Cross-reactive epitopes from various proteins of SARS-CoV-2 and LAVs were also identified (15 epitopes from BCG, 7 epitopes from MMR, but none from OPV). A majority of the identified epitopes were observed to belong to ORF1ab, further suggesting the vital role of ORF1ab in the coronaviruses family and suggesting it as a candidate for a potential universal coronavirus vaccine that protects against severe disease by inducing cell mediated immunity.


Subject(s)
COVID-19 , Common Cold , Middle East Respiratory Syndrome Coronavirus , Viral Vaccines , Humans , SARS-CoV-2/genetics , Epitopes, T-Lymphocyte , Middle East Respiratory Syndrome Coronavirus/genetics , Vaccines, Attenuated , COVID-19 Vaccines , COVID-19/prevention & control , Alleles , BCG Vaccine , Indonesia/epidemiology , Spike Glycoprotein, Coronavirus/genetics
19.
Biology (Basel) ; 11(10)2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2081964

ABSTRACT

During the last two years, the emergence of SARS-CoV-2 has led to millions of deaths worldwide, with a devastating socio-economic impact on a global scale. The scientific community's focus has recently shifted towards the association of the T cell immunological repertoire with COVID-19 progression and severity, by utilising T cell receptor sequencing (TCR-Seq) assays. The Multiplexed Identification of T cell Receptor Antigen (MIRA) dataset, which is a subset of the immunoACCESS study, provides thousands of TCRs that can specifically recognise SARS-CoV-2 epitopes. Our study proposes a novel Machine Learning (ML)-assisted approach for analysing TCR-Seq data from the antigens' point of view, with the ability to unveil key antigens that can accurately distinguish between MIRA COVID-19-convalescent and healthy individuals based on differences in the triggered immune response. Some SARS-CoV-2 antigens were found to exhibit equal levels of recognition by MIRA TCRs in both convalescent and healthy cohorts, leading to the assumption of putative cross-reactivity between SARS-CoV-2 and other infectious agents. This hypothesis was tested by combining MIRA with other public TCR profiling repositories that host assays and sequencing data concerning a plethora of pathogens. Our study provides evidence regarding putative cross-reactivity between SARS-CoV-2 and a wide spectrum of pathogens and diseases, with M. tuberculosis and Influenza virus exhibiting the highest levels of cross-reactivity. These results can potentially shift the emphasis of immunological studies towards an increased application of TCR profiling assays that have the potential to uncover key mechanisms of cell-mediated immune response against pathogens and diseases.

20.
Viruses ; 14(10)2022 10 19.
Article in English | MEDLINE | ID: covidwho-2081879

ABSTRACT

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Humans , Antibodies, Viral , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Immunity , Immunoglobulin A , Immunoglobulin G , Organ Transplantation/adverse effects , SARS-CoV-2
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