Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 121
Filter
1.
Transpl Immunol ; 74: 101670, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1984170

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated. METHODS: In the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16-21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose. RESULTS: Overall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed. CONCLUSION: The current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients.


Subject(s)
COVID-19 , SARS-CoV-2 , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Graft Rejection , HLA Antigens/genetics , Histocompatibility Antigens , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Humans , RNA, Messenger , Renal Dialysis , Vaccination , rho Guanine Nucleotide Dissociation Inhibitor beta
2.
Transpl Int ; 35: 10626, 2022.
Article in English | MEDLINE | ID: covidwho-1974701

ABSTRACT

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.


Subject(s)
COVID-19 , Kidney Transplantation , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines/therapeutic use , Graft Rejection , HLA Antigens , Humans , Pandemics , SARS-CoV-2 , Transplant Recipients , Vaccination
3.
Transpl Immunol ; 74: 101656, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1967189

ABSTRACT

Advances in immune suppression therapies and desensitization have made possible kidney transplantation regardless of HLA incompatibility. Single antigen bead assay (SAB) is a semi-quantitative estimation of the amount of human leukocyte antigen (HLA) antibodies present in the recipient plasma, and mean fluorescence intensity (MFI) generated gives this rough estimation of the antibodies present in the recipient. Here we present a case of successful kidney transplantation in a patient who expressed DSA with high MFI. A 33-yr-old male, diagnosed with chronic kidney disease (CKD) on regular maintenance hemodialysis, opted for second kidney transplant with his sibling as prospective donor and was referred to the department of Transplant Immunology for histocompatibility testing. Patient had HLA incompatibility with multiple DSA identified by SAB. Patient undergone 20 sessions of plasma exchange till discharge and finally till 6 months graft was functioning well. The authors thus conclude that the option of a high-risk HLA incompatible kidney transplant can be offered to recipients with high MFI DSA, who wish to undergo transplantation for end stage renal disease.


Subject(s)
Kidney Transplantation , Graft Rejection/therapy , Graft Survival , HLA Antigens , Histocompatibility Testing , Humans , Male , Plasma Exchange , Retrospective Studies
4.
Phys Chem Chem Phys ; 24(27): 16876-16883, 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1921736

ABSTRACT

The COVID-19 epidemic, caused by virus SARS-CoV-2, has turned into a pandemic and threatened everyone's health for the past two years. In SARS-CoV-2, ORF8 is one of the most important accessory proteins with a role in immune modulation. There are multiple disulfide bonds in the wild type (WT) ORF8. Here, we present an in silico study on the effects of the disulfide bonds in ORF8 on the aspects of the structural properties and binding properties with the human leukocyte antigen (HLA-A). We first define five possible states for ORF8 with different disulfide bond reduction schemes. For each state, we collect the conformational ensemble using molecular dynamics (MD) simulations in an explicit solvent. From the analysis of the structural properties, we find that the reduction of the disulfide bonds has small effects on the global properties but much larger effects on the ORF8-specific region that is located on the surface of the ORF8 dimer. Interestingly, we find that the dimer does not break into two monomers at room temperature even if all the disulfide bonds get reduced. Further, we investigate the role of the disulfide bonds in the interactions with the human leukocyte antigen (HLA) by performing docking between HLA-A and the conformational ensembles of ORF8 in different states. We give predictions on the preferred binding sites for each state and validate the predictions for the WT dimer with the experimental data on epitopes. In the end, we evaluate the stability of the complexes formed between HLA-A and ORF8 in each state using MD simulations. Our observations can provide inspiration for inhibitor/drug design against ORF8 based on the binding pathway with HLA-A.


Subject(s)
COVID-19 , SARS-CoV-2 , Viral Proteins/metabolism , Disulfides , HLA Antigens , HLA-A Antigens , Humans
5.
J Immunol Res ; 2022: 9710376, 2022.
Article in English | MEDLINE | ID: covidwho-1874908

ABSTRACT

The human leukocyte antigen (HLA) system is one of the most crucial host factors influencing disease progression in bacterial and viral infections. This review provides the basic concepts of the structure and function of HLA molecules in humans. Here, we highlight the main findings on the associations between HLA class I and class II alleles and susceptibility to important infectious diseases such as tuberculosis, leprosy, melioidosis, Staphylococcus aureus infection, human immunodeficiency virus infection, coronavirus disease 2019, hepatitis B, and hepatitis C in populations worldwide. Finally, we discuss challenges in HLA typing to predict disease outcomes in clinical implementation. Evaluation of the impact of HLA variants on the outcome of bacterial and viral infections would improve the understanding of pathogenesis and identify those at risk from infectious diseases in distinct populations and may improve the individual treatment.


Subject(s)
COVID-19 , Alleles , COVID-19/genetics , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class II , Humans
6.
Cell Rep ; 39(11): 110952, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866957

ABSTRACT

Sequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can affect T cell response in COVID-19. We studied T cell responses to SARS-CoV-2 and HCoVs in convalescent COVID-19 donors and identified a highly conserved SARS-CoV-2 sequence, S811-831, with overlapping epitopes presented by common MHC class II proteins HLA-DQ5 and HLA-DP4. These epitopes are recognized by low-abundance CD4 T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. T cell cross-reactivity is driven by the high conservation across human and animal coronaviruses of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC class II binding preferences and substitutions at secondary TCR contact sites. These data highlight S811-831 as a highly conserved CD4 T cell epitope broadly recognized across human populations.


Subject(s)
COVID-19 , SARS-CoV-2 , Alleles , CD4-Positive T-Lymphocytes , COVID-19 Vaccines , Epitopes, T-Lymphocyte , HLA Antigens , Humans , Receptors, Antigen, T-Cell , mRNA Vaccines
7.
Front Immunol ; 13: 812393, 2022.
Article in English | MEDLINE | ID: covidwho-1858006

ABSTRACT

CD8+ T cells are a pivotal part of the immune response to viruses, playing a key role in disease outcome and providing long-lasting immunity to conserved pathogen epitopes. Understanding CD8+ T cell immunity in humans is complex due to CD8+ T cell restriction by highly polymorphic Human Leukocyte Antigen (HLA) proteins, requiring T cell epitopes to be defined for different HLA allotypes across different ethnicities. Here we evaluate strategies that have been developed to facilitate epitope identification and study immunogenic T cell responses. We describe an immunopeptidomics approach to sequence HLA-bound peptides presented on virus-infected cells by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using antigen presenting cell lines that stably express the HLA alleles characteristic of Indigenous Australians, this approach has been successfully used to comprehensively identify influenza-specific CD8+ T cell epitopes restricted by HLA allotypes predominant in Indigenous Australians, including HLA-A*24:02 and HLA-A*11:01. This is an essential step in ensuring high vaccine coverage and efficacy in Indigenous populations globally, known to be at high risk from influenza disease and other respiratory infections.


Subject(s)
Influenza Vaccines , Influenza, Human , Australia , CD8-Positive T-Lymphocytes , Chromatography, Liquid , Epitopes, T-Lymphocyte , HLA Antigens , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Humans , Tandem Mass Spectrometry
8.
Curr Opin Immunol ; 76: 102178, 2022 06.
Article in English | MEDLINE | ID: covidwho-1828141

ABSTRACT

The extraordinary variation of the human leukocyte antigen (HLA) molecules is critical for diversifying antigen presentation to T cells. Coupled with the rise of novel strains and rapidly evolving immune evasion by SARS-CoV-2 proteins, HLA-mediated immunity in COVID-19 is critically important but far from being fully understood. A growing number of studies have found the association of HLA variants with different COVID-19 outcomes and that HLA genotypes associate with differential immune responses against SARS-CoV-2. Prediction studies have shown that mutations in multiple viral strains, most concentrated in the Spike protein, affect the affinity between these mutant peptides and HLA molecules. Understanding the impact of this variation on T-cell responses is critical for comprehending the immunogenic mechanisms in both natural immunity and vaccine development.


Subject(s)
COVID-19 , Antigen Presentation , Epitopes, T-Lymphocyte , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class II , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
9.
HLA ; 100(1): 52-58, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1816658

ABSTRACT

The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.


Subject(s)
COVID-19 , Kidney Transplantation , Alleles , Antibodies , COVID-19 Vaccines , Flow Cytometry , Graft Rejection , Graft Survival , HLA Antigens , Humans , Living Donors , Male , Middle Aged , SARS-CoV-2 , Vaccination
10.
Stem Cell Reports ; 17(4): 711-714, 2022 04 12.
Article in English | MEDLINE | ID: covidwho-1756288

ABSTRACT

The manipulation of human leukocyte antigens (HLAs) and immune modulatory factors in "universal" human pluripotent stem cells (PSCs) holds promise for immunological tolerance without HLA matching. This paradigm raises concerns should "universal" grafts become virally infected. Furthermore, immunological manipulation might functionally impair certain progeny, such as hematopoietic stem cells. We discuss the risks and benefits of hypoimmunogenic PSCs, and the need to further advance HLA matching and autologous strategies.


Subject(s)
Pandemics , Pluripotent Stem Cells , HLA Antigens , Humans , Stem Cell Transplantation/adverse effects
11.
Eur J Hum Genet ; 30(8): 922-929, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1758186

ABSTRACT

The human leucocyte antigen (HLA) loci have been widely characterized to be associated with viral infectious diseases using either HLA allele frequency-based association or in silico predicted studies. However, there is less experimental evidence to link the HLA alleles with COVID-19 and other respiratory infectious diseases, particularly in the lung cells. To examine the role of HLA alleles in response to coronavirus and other respiratory viral infections in disease-relevant cells, we designed a two-stage study by integrating publicly accessible RNA-seq data sets, and performed allelic expression (AE) analysis on heterozygous HLA genotypes. We discovered an increased AE pattern accompanied with overexpression of HLA-B gene in SARS-CoV-2-infected human lung epithelial cells. Analysis of independent data sets verified the respiratory virus-induced AE of HLA-B gene in lung cells and tissues. The results were further experimentally validated in cultured lung cells infected with SARS-CoV-2. We further uncovered that the antiviral cytokine IFNß contribute to AE of the HLA-B gene in lung cells. Our analyses provide a new insight into allelic influence on the HLA expression in association with SARS-CoV-2 and other common viral infectious diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Allelic Imbalance , COVID-19/genetics , HLA Antigens/genetics , HLA-B Antigens/genetics , Histocompatibility Antigens Class I/genetics , Humans , Lung
12.
Hum Immunol ; 83(1): 1-9, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1719801

ABSTRACT

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies.


Subject(s)
COVID-19/genetics , HLA Antigens/genetics , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Female , Gene Frequency , Genetic Predisposition to Disease , HLA Antigens/immunology , Haplotypes , Host-Pathogen Interactions , Humans , Male , Middle Aged , Protective Factors , Risk Assessment , Risk Factors , SARS-CoV-2/pathogenicity , Severity of Illness Index , United Arab Emirates , Young Adult
13.
Int J Mol Sci ; 23(5)2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1715409

ABSTRACT

We propose a new hypothesis that explains the maintenance and evolution of MHC polymorphism. It is based on two phenomena: the constitution of the repertoire of naive T lymphocytes and the evolution of the pathogen and its impact on the immune memory of T lymphocytes. Concerning the latter, pathogen evolution will have a different impact on reinfection depending on the MHC allomorph. If a mutation occurs in a given region, in the case of MHC allotypes, which do not recognize the peptide in this region, the mutation will have no impact on the memory repertoire. In the case where the MHC allomorph binds to the ancestral peptides and not to the mutated peptide, that individual will have a higher chance of being reinfected. This difference in fitness will lead to a variation of the allele frequency in the next generation. Data from the SARS-CoV-2 pandemic already support a significant part of this hypothesis and following up on these data may enable it to be confirmed. This hypothesis could explain why some individuals after vaccination respond less well than others to variants and leads to predict the probability of reinfection after a first infection depending upon the variant and the HLA allomorph.


Subject(s)
COVID-19/immunology , HLA Antigens/immunology , Polymorphism, Genetic/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , COVID-19/epidemiology , COVID-19/virology , Evolution, Molecular , Gene Frequency , HLA Antigens/genetics , HLA Antigens/metabolism , Humans , Immunity, Innate/genetics , Immunity, Innate/immunology , Mutation/genetics , Mutation/immunology , Pandemics , Peptides/immunology , Peptides/metabolism , Polymorphism, Genetic/genetics , SARS-CoV-2/physiology , T-Lymphocytes/cytology , T-Lymphocytes/metabolism
14.
PLoS Pathog ; 18(2): e1010339, 2022 02.
Article in English | MEDLINE | ID: covidwho-1686116

ABSTRACT

Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment.


Subject(s)
HLA Antigens/immunology , Immunotherapy, Adoptive , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Epitopes, T-Lymphocyte , Female , HEK293 Cells , Humans , Immunophenotyping , Male , Middle Aged , Young Adult
15.
Front Immunol ; 13: 752622, 2022.
Article in English | MEDLINE | ID: covidwho-1686481

ABSTRACT

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ+ T cells after mixed COVID-19 convalescent patients' peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Spike Glycoprotein, Coronavirus/immunology , Female , HLA Antigens/genetics , Humans , Male , SARS-CoV-2/immunology
16.
HLA ; 99(4): 281-312, 2022 04.
Article in English | MEDLINE | ID: covidwho-1642778

ABSTRACT

HLA is crucial for appropriate immune responses in several viral infections, as well as in severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The unpredictable nature of Coronavirus Disease 19 (COVID-19), observed in both inter-individual and inter-population level, raises the question, to what extent the HLA, as part of host genetic factors, contribute to disease susceptibility and prognosis. We aimed to identify significant HLAs, those were investigated till now, for their association with COVID-19. Three databases were searched (PubMed, Cochrane library, and Web of Science) and articles published between January 2020 and May 2021 were included for in-depth analysis. Two separate teams including four observers independently extracted the summary data, with discrepancies resolved by consensus. This study is registered with PROSPERO (CRD42021251670). Of 1278 studies identified, 36 articles were included consisting of 794,571 participants. Countries from the European region appeared in the highest number of studies and vice versa for countries from South East Asia. Among 117 significantly altered alleles, 85 (72.65%) were found to have a positive correlation with COVID-19 and 33 (27.35%) alleles were observed having a negative correlation. HLA A*02 is the most investigated allele (n = 18) and showed contradictory results. Non-classical HLA E was explored by only one study and it showed that E*01:01 is associated with severity. Both in silico and wet lab data were considered and contrasting results were found from two approaches. Although several HLAs depicted significant association, nothing conclusive could be drawn because of heterogeneity in study designs, HLA typing methods, and so forth. This systematic review shows that, though HLAs play role in COVID-19 susceptibility, severity, and mortality, more uniformly designed, interrelated studies with the inclusion of global data, for use in evidence-based medicine are needed.


Subject(s)
COVID-19 , Alleles , COVID-19/genetics , HLA Antigens/genetics , Humans , Polymorphism, Genetic , SARS-CoV-2
17.
EBioMedicine ; 73: 103679, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1595805

ABSTRACT

BACKGROUND: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. METHODS: We performed a prospective longitudinal study in sixty-one KT recipients given three doses of the BNT162b2 COVID-19 vaccine. We performed semi-structured pharmacovigilance interviews and monitored donor-specific antibodies and kidney function. We compared levels of anti-spike IgG, pseudo-neutralization activity against vaccine homologous and heterologous variants, frequency of spike-specific interferon (IFN)-γ-secreting cells, and antigen-induced cytokine production 28 days after the second and third doses. FINDINGS: Reactions to vaccine were mild. One patient developed donor-specific anti-HLA antibodies after the second dose which could be explained by non-adherence to immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) after the second dose to 62·3% (n=38) after the third dose (p<0·05). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific IFN-γ-secreting cells increased from 19·9 (SD, 56·0) to 64·0 (SD, 76·8) cells/million PBMCs after the third dose (p<0·0001). A significant increase in IFN-γ responses was also observed in patients who remained seronegative after three doses (p<0·0001). INTERPRETATION: A third dose of the BNT162b2 vaccine increases both cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. FUNDING: Nice University Hospital, University Cote d'Azur.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Kidney Transplantation , Aged , Antibodies, Neutralizing/blood , Autoantibodies/blood , /adverse effects , COVID-19/prevention & control , COVID-19/virology , Female , Graft Rejection/prevention & control , HLA Antigens/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunosuppressive Agents/therapeutic use , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Longitudinal Studies , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology
18.
Hematology Am Soc Hematol Educ Program ; 2021(1): 190-195, 2021 12 10.
Article in English | MEDLINE | ID: covidwho-1582134

ABSTRACT

In case 1, a 14-month-old male child with sickle cell disease (SCD) was referred for evaluation for an allogeneic hematopoietic stem cell transplant (HCT). The patient had a history of dactylitis 3 times in his first year of life and febrile episodes twice at the consult. His 4-year-old sister was found to be human leukocyte antigen (HLA) identical. The patient was started on hydroxyurea (HU) at 2.5 years of age. His parents again sought consultation when he was 5 years old because of concerns about his medical condition. At the time, the patient had experienced 2 vaso-occlusive pain episodes (VOEs) requiring hospitalization during the previous 2 years. He had also experienced intermittent pain crises requiring rest at home for 2 to 3 days. The child has not attended school in person due to the COVID-19 pandemic. The family is considering HCT but is ambivalent about it because of potential toxicity. In case 2, an 8-year-old female child is 3 years out from HCT for SCD from her HLA-identical sibling. Before HCT, despite receiving HU, she had experienced >5 VOEs requiring hospitalization and 2 episodes of acute chest syndromes in the previous 3 years. She had also been missing almost 50 days of school days each year. After HCT, she is now attending school regularly and participating in all normal age-appropriate activities. The parents believe that HCT has been transformative in their child's life.


Subject(s)
Anemia, Sickle Cell/therapy , Hematopoietic Stem Cell Transplantation , Age Factors , Anemia, Sickle Cell/epidemiology , Child , Child, Preschool , Evidence-Based Medicine , Female , HLA Antigens/analysis , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Male , Quality of Life , Risk Factors , Siblings , Tissue Donors
20.
Viruses ; 13(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1554986

ABSTRACT

In the last two years, we have been struggling with the pandemic of SARS-CoV-2, the virus causing COVID-19. Several cases of subacute thyroiditis (SAT) have already been described as directly related to SARS-CoV-2 infection. The clinical course of SAT induced by SARS-CoV-2 can be entirely different from the classic SAT course, and one of the most important differences is a very rapid SAT onset observed in some patients, especially a phenomenon of the simultaneous presence of both diseases. The aim of this report is to compare HLA profile and clinical course of SAT in four patients, in whom SAT was considered as triggered by COVID-19, with special attention paid to the differences between a patient with rare simultaneous presence of SAT and COVID-19, and patients with longer time lag between the diseases. The unusual phenomenon of simultaneous occurrence of COVID-19 and SAT induced by SARS-CoV-2 infection can be HLA-dependent and related to the presence of homozygosity at HLA-B*35. Additionally, the clinical course of SAT triggered by COVID-19 can be HLA-related in regard to the risk of recurrence, and to a variety of other aspects, including severity of thyrotoxicosis.


Subject(s)
COVID-19/immunology , HLA Antigens , Thyroiditis, Subacute/etiology , Thyroiditis, Subacute/immunology , Adult , COVID-19/physiopathology , Female , HLA-B35 Antigen , Humans , Male , Middle Aged , SARS-CoV-2 , Thyroiditis, Subacute/physiopathology
SELECTION OF CITATIONS
SEARCH DETAIL