RESUMO
Purpose: This study analyses the immune response of elite athletes after COVID-19 vaccination with double-dose mRNA and a single-dose vector vaccine. Methods: Immunoglobulin G (IgG) antibody titers, neutralizing activity, CD4 and CD8 T-cells were examined in blood samples from 72 athletes before and after vaccination against COVID-19 (56 mRNA (BNT162b2 / mRNA-1273), 16 vector (Ad26.COV.2) vaccines). Side effects and training time loss was also recorded. Results: Induction of IgG antibodies (mRNA : 5702 BAU/ml ; 4343 BAU/ml (hereafter: median), vector: 61 BAU/ml ; 52 BAU/ml, p<0.01), their neutralizing activity (99.7% ; 10.6%, p<0.01), and SARS-CoV-2 spike-specific CD4 T-cells (0.13% ; 0.05% ; p<0.01) after mRNA double-dose vaccines was significantly more pronounced than after a single-dose vector vaccine. SARS-CoV-2 spike-specific CD8 T-cell levels after a vector vaccine (0.15%) were significantly higher than after mRNA vaccines (0.02%; p<0.01). When athletes who had initially received the vector vaccine were boostered with an mRNA vaccine, IgG antibodies (to 3456 BAU/ml; p<0.01), neutralizing activity (to 100%; p<0.01), CD4 (to 0.13%; p<0.01) and CD8 T-cells (to 0.43%; p<0.01) significantly increased. When compared with dual-dose mRNA regimen, IgG antibody response was lower (p<0.01), the neutralizing activity (p<0.01) and CD8 T-cell (p<0.01) response higher and no significant difference in CD4 T-cell response (p=0.54) between the two regimens. Cumulative training loss (3 days) did not significantly differ between vaccination regimens (p=0.46). Conclusion: mRNA and vector vaccines against SARSCoV-2 appear to induce different patterns of immune response in athletes. Lower immune induction after a single-shot vector vaccine was clearly optimized by a heterologous booster. Vaccine reactions were mild and short-lived.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Atletas , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Vacinação , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Masculino , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Imunoglobulina G/sangue , Anticorpos Neutralizantes/sangue , Feminino , Adulto , Linfócitos T CD4-Positivos/imunologia , Adulto Jovem , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
BACKGROUND: Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. METHODS: In this observational study, pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. RESULTS: Patients with PFP were more often HSV-seropositive than controls (p = 0.0003), whereas VZV- and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile of borrelia-specific T cells was also found in a patient with acute neuroborreliosis. DISCUSSION: In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.
Assuntos
Paralisia Facial , Herpes Zoster , Humanos , Antígeno CTLA-4 , Imunidade Humoral , Antígeno Ki-67 , Herpesvirus Humano 3 , SimplexvirusRESUMO
Self-taking oropharyngeal swabs for sexually transmitted infections such as gonorrhoea and chlamydia has become more common during the COVID-19 pandemic to minimise the risk to healthcare workers. However, there have been no standardised guidelines on sampling time for taking an oropharyngeal swab for gonorrhoea and chlamydia testing. We recruited 215 participants at the Melbourne Sexual Health Centre, Australia, between November 2021 and January 2022. We asked participants to report the time they spent on self-taking the oropharyngeal swab. The median self-taking sampling time was 8s (IQR=5-12), and the time did not differ between oropharyngeal gonorrhoea positivity (P =0.570) and oropharyngeal chlamydia positivity (P =0.457).
Assuntos
COVID-19 , Infecções por Chlamydia , Gonorreia , Masculino , Humanos , Gonorreia/epidemiologia , Pandemias , Homossexualidade Masculina , Manejo de Espécimes , Infecções por Chlamydia/epidemiologia , Neisseria gonorrhoeaeRESUMO
BACKGROUND: Current international guidelines on human immunodeficieny virus (HIV) Pre-Exposure Prophylaxis (PrEP) recommend serological screening for syphilis at routine 3-monthly PrEP appointments. The aim of our study was to describe the pattern of clinical presentation of syphilis among men who have sex with men (MSM) taking PrEP. We were interested in whether syphilis is detected through screening at scheduled3-monthly PrEP clinic appointments or whether primary or secondary syphilis presented at unscheduled interval visits. METHODS: This was a retrospective study of MSM attending the PrEP clinic at the Melbourne Sexual Health Centre between February 2016 and March 2019. Serological screening for syphilis was routinely undertaken at 3-monthly PrEP clinic appointments. Diagnoses of early syphilis were identified from PrEP clinic visits and from interim walk-in STI clinic attendances. RESULTS: There were 69 cases of early syphilis among 61 MSM taking PrEP during the study period. There were 24 (35%) primary, 16 (23%) secondary, and 29 (42%) early latent infections. The incidence of early syphilis was 8.6 per 100 person-years. A substantial proportion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments. CONCLUSIONS: Syphilis screening at routine 3-monthly PrEP visits alone fails to detect a proportion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission. Education of MSM taking PrEP regarding the risk of syphilis and symptom recognition is necessary together with access to syphilis testing between PrEP visits.
Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Austrália/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Estudos Retrospectivos , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/prevenção & controleRESUMO
Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2-specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2-specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2-specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2-specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.
Assuntos
COVID-19 , Transplante de Órgãos , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , Imunidade Celular , Imunidade Humoral , RNA Mensageiro/genética , SARS-CoV-2 , TransplantadosRESUMO
Compliance of elite athletes with vaccination recommendations is low mainly based on concerns about side-effects and perceived poor vaccine efficacy due to continued physical training. We therefore employed seasonal influenza vaccination to investigate the effect of regular physical training on vaccine-induced cellular and humoral immunity in elite athletes and controls. Lymphocyte subpopulations and vaccine-specific T-cells were quantified and functionally characterized from 45 athletes and 25 controls before, and 1, 2 and 26â¯weeks after vaccination. Moreover, influenza-specific antibodies and their neutralizing function were quantified. Both groups showed a significant increase in vaccine-reactive CD4 T-cell levels which peaked one week after vaccination (pâ¯<â¯0.0001). The increase was significantly more pronounced in athletes (4.1-fold) compared to controls (2.3-fold; pâ¯=â¯0.0007). The cytokine profile changed from multifunctional T-cells co-producing IFNγ, IL-2 and TNFα to cells with restricted cytokine expression. This change in functionality was associated with a significant increase in CTLA-4 expression (pâ¯<â¯0.0001), which again was more pronounced in athletes. Likewise, the increase in neutralizing antibodies was stronger in athletes (pâ¯=â¯0.004 for H1N1; pâ¯=â¯0.032 for H3N2). In conclusion, both groups mounted a strong vaccine-specific cellular and humoral immunity after standard vaccination. The more pronounced increase in specific T-cells and neutralizing antibodies indicates that high frequency and intensity of training enhance vaccine-responses in elite athletes.
Assuntos
Anticorpos Antivirais/imunologia , Atletas , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Linfócitos T/imunologia , Anticorpos Neutralizantes/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/prevenção & controle , Masculino , Vacinação , Adulto JovemRESUMO
VZV-reactivation may lead to symptomatic central nervous system (CNS) diseases, but identification of VZV as causative pathogen of CNS-diseases is challenging. This study was performed to characterize VZV-specific T cells from cerebrospinal fluid (CSF) and blood of patients with active CNS-disease and to determine whether this may improve differential diagnosis. 27 patients with pleocytosis in the CSF were recruited and classified into three groups (10 VZV-related, 10 non-VZV-related, 7 unclear). VZV-specific CD4+ T cells were quantified in CSF and blood after simultaneous stimulation with a VZV-antigen lysate and detection of cytokines (IFN-γ, IL-2, TNF-α) and CTLA-4. Polyclonal stimulation served as positive control. VZV-specific CD4+ T-cell frequencies were highest in both CSF (p = 0.0001) and blood (p = 0.011) of patients with VZV-infection, and were enriched at the site of infection (p = 0.002). While cytokine-expression profiles only showed minor differences between the groups, CTLA-4-expression levels on VZV-specific T cells from CSF and blood were significantly increased in VZV-related CNS-infections (p = 0.0002 and p<0.0001) and clearly identified VZV-related CNS-diseases (100% sensitivity and 100% specificity). Polyclonally stimulated T cells did not show any quantitative and phenotypical differences between the groups. Increased frequency and CTLA-4-expression of VZV-specific T cells from CSF or blood are specifically found in patients with VZV-related CNS-infection.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígeno CTLA-4/biossíntese , Infecções do Sistema Nervoso Central/virologia , Herpesvirus Humano 3/imunologia , Imunidade Celular/imunologia , Adulto , Sangue/virologia , Infecções do Sistema Nervoso Central/imunologia , Líquido Cefalorraquidiano/virologia , Feminino , Herpesvirus Humano 3/metabolismo , Humanos , Interferon gama/sangue , Interleucina-2/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Ativação Viral/imunologiaRESUMO
In this approach, pre-stained cells from extrasanguinous fluids (ESFs) are stimulated in the presence of blood from the same individual. Thus, blood-derived antigen-presenting cells enable stimulation of both ESF- and blood T cells. Pre-staining allows distinction of T cells from ESF and blood, and simultaneous analysis of antigen-specific T cells in both compartments.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Herpesvirus Humano 3/imunologia , Imunoensaio/métodos , Meningite Viral/diagnóstico , Linfócitos T/imunologia , Adulto , Líquido Cefalorraquidiano/citologia , Humanos , Meningite Viral/imunologia , Meningite Viral/virologia , Mycobacterium tuberculosis/imunologia , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/virologia , Recidiva , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologiaRESUMO
OBJECTIVE: As reconstitution of virus-specific T-cells is critical to control cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we characterized the dynamics in CMV-specific T-cell reconstitution after SCT. METHODS: Cytomegalovirus-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I-specific pentamers using flow cytometry. RESULTS: Cytomegalovirus-specific CD4 T-cells reconstituted after a median of 2.3 (IQR, 2.0-3.0) weeks following autografting, and 4.0 (IQR, 3.0-5.6) weeks after allografting, with CMV-specific T-cells originating from donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8 T-cells did not differ (P = .58). Factors delaying the time to initial reconstitution of CMV-specific CD4 T-cells included a negative recipient serostatus (P = .016) and CMV-viremia (P = .026). Percentages of CMV-specific CD4 T-cells significantly increased over time and reached a plateau after 90 days (P = .043). Relative CMV-specific CD4 T-cell levels remained higher in long-term transplant recipients compared with those in controls (P < .0001). However, due to persisting lymphopenia, absolute numbers of CMV-specific T-cells were similar as in controls. CONCLUSION: Cytomegalovirus-specific T-cells rapidly reconstitute after SCT and their percentages remain high in the long term. In the face of persistent lymphopenia, this results in similar absolute numbers of CMV-specific T-cells as in controls to ensure sufficient pathogen control.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Linfopenia/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Reconstituição Imune , Contagem de Linfócitos , Linfopenia/patologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Transplante Autólogo , Transplante HomólogoRESUMO
Background: Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited. Methods: Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses. Results: Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Conclusions: Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.
Assuntos
Síndrome de Down/imunologia , Imunidade Celular/imunologia , Adolescente , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Criança , Citomegalovirus/imunologia , Feminino , Herpesvirus Humano 3/imunologia , Humanos , Masculino , FenótipoRESUMO
BACKGROUND: Varicella zoster virus (VZV) establishes lifelong persistence and may reactivate in individuals with impaired immune function. To investigate immunologic correlates of protection and VZV reactivation, we characterized specific immunity in 207 nonsymptomatic immunocompetent and 132 immunocompromised individuals in comparison with patients with acute herpes zoster. METHODS: VZV-specific CD4 T cells were quantified flow cytometrically after stimulation and characterized for expression of interferon-γ, interleukin 2, and tumor necrosis factor α and surface markers for differentiation (CD127) and anergy (cytotoxic T lymphocyte antigen 4 [CTLA-4] and programmed death [PD]-1). Immunoglobulin G and A levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: In healthy individuals, VZV-specific antibody and T-cell levels were age dependent, with the highest median VZV-specific CD4 T-cell frequencies of 0.108% (interquartile range, 0.121%) during adolescence. VZV-specific T-cell profiles were multifunctional with predominant expression of all 3 cytokines, CD127 positivity, and low expression of CTLA-4 and PD-1. Nonsymptomatic immunocompromised patients had similar VZV-specific immunologic properties except for lower T-cell frequencies (P<.001) and restricted cytokine expression. In contrast, significantly elevated antibody- and VZV-specific CD4 T-cell levels were found in patients with zoster. Their specific T cells showed a shift in cytokine expression toward interferon γ single positivity, an increase in CTLA-4 and PD-1, and a decrease in CD127 expression (all P<.001). This phenotype normalized after resolution of symptoms. CONCLUSIONS: VZV-specific CD4-T cells in patients with zoster bear typical features of anergy. This phenotype is reversible and may serve as adjunct tool for monitoring VZV reactivations in high-risk patients.
Assuntos
Herpes Zoster/epidemiologia , Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Imunidade Celular/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Células Cultivadas , Criança , Pré-Escolar , Citocinas/análise , Citocinas/imunologia , Feminino , Herpes Zoster/virologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Linfócitos T/imunologia , Adulto JovemRESUMO
Serological identification of the cytomegalovirus (CMV) status in children less than 18 months of age is complicated by the variable persistence of maternal antibodies. As T cells are not passively transferred, we attempted to assess whether CMV-specific cellular immunity may be superior to determine the actual CMV status; we also performed a functional characterization of T-cell immunity in childhood. Antibodies from 59 mothers and 168 children were determined, and specific CD4(+) T cells were identified by induction of IFN-γ, IL-2, TNF-α, IL-4, and IL-17 after CMV-specific and polyclonal stimulation. Agreement between both tests was perfect for mothers and children more than 18 months. Among infants less than 18 months, 17/30 were concordantly negative. Interestingly, 8/13 seropositive children had detectable CMV-specific T cells, whereas only 5/13 were T-cell negative, indicating passive immunity. CMV-specific T cells from young infants differed in cytokine profiles from that of older age groups, and polyclonal effector T-cell frequencies were higher in young infants with detectable CMV-specific T cells compared with those without. In conclusion, the majority of young infants with CMV-specific antibodies show evidence of true infection, which indicates that passive immunity is overestimated. Our data may have important implications for improved risk stratification and CMV management in infants in the setting of transplantation.
Assuntos
Anticorpos Antivirais/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunidade Materno-Adquirida , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Citocinas/biossíntese , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lactente , Recém-Nascido , Interferon gama/biossíntese , Interferon gama/imunologia , Masculino , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismoRESUMO
OBJECTIVE: Apheresis treatment (AT) is an established standard of treatment in various neurological autoimmune diseases. Since not all patients equally benefit from AT, we saw the need to investigate the effect of different clinical, paraclinical and technical-apparative factors on the clinical outcome. Additionally, we wanted to find out whether patients who improved due to AT continue to be clinically stable under B-cell depletion (BCD). METHODS: We screened all patients (n = 358) with neurological diseases who received AT at the Medical center of the University of the Saarland in the past 20 years. Different factors (e.g., age, sex, duration until onset of AT, type of AT, number of cycles, csf parameters) were analyzed retrospectively. Clinical disability was measured using the modified Rankin scale (mRS), visual acuity and the Expanded Disability Status Scale (EDSS). RESULTS: 335 patients, categorized into 11 different autoimmune diagnosis groups, received a total of 2669 treatment cycles and showed a statistically significant improvement in mRS with AT (p < 0.001). Patients in American Society for Apheresis (ASFA) categories I (p = 0.013) and II (p = 0.035) showed a significantly greater benefit under AT than those in category III. The clinical outcome was better with shorter duration until AT onset, more cycles of AT, and more plasma volume exchanged and the presence of an autoimmune antibody. Patients who initially profited had a significantly more stable course of the disease after 1-Year-BCD (p = 0.039). DISCUSSION: In the present study, we were able to identify various significant factors influencing the outcome of patients due to AT. Furthermore, we could show that patients with a response to AT can benefit from BCD follow-up therapy.
Assuntos
Remoção de Componentes Sanguíneos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Remoção de Componentes Sanguíneos/métodos , Idoso , Resultado do Tratamento , Doenças Autoimunes do Sistema Nervoso/terapia , Doenças Autoimunes do Sistema Nervoso/imunologia , Seguimentos , Linfócitos B/imunologia , Adulto Jovem , Adolescente , Doenças do Sistema Nervoso/terapia , Doenças Autoimunes/terapia , Depleção Linfocítica/métodos , Idoso de 80 Anos ou maisRESUMO
Knowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection. In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron-subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination. The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4+ and CD8+ T-cell levels. Neutralizing activity towards the parental strain was higher than towards the Omicron-subvariants, whereas specific T-cell levels towards parental spike and Omicron-subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4+ T-cell levels with lower CTLA-4 expression compared to infection-naive patients. When compared to controls, no differences were observed between infection-naive individuals. Among convalescent individuals, CD4+ T-cell levels were higher in patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among patients. In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4+ T cells, which may reflect prolonged encounter with antigen during infection.
RESUMO
Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Imunidade Humoral , Infecções Irruptivas , COVID-19/prevenção & controle , Vacinação , Vacinas Combinadas , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
Antigen-specific antibodies are well characterized after vaccination with pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular immunity toward pandemic H1N1 after vaccination and infection and cross-reactivities toward seasonal antigens is limited. Nineteen individuals were vaccinated with the pandemic H1N1 vaccine. Among those, ten had been prevaccinated against seasonal influenza. CD4(+) T cells specific for pandemic H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry and ELISA/neutralization assays, respectively. In addition, seven patients with acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination induced a strong 4.63-fold (IQR 4.16) increase in antigen-specific CD4(+) T cells that was more pronounced in individuals not prevaccinated with seasonal influenza (p = 0.01). T-cell levels toward seasonal vaccine concomitantly rose by 2.71-fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a less pronounced increase in specific antibodies. Influenza-specific T cells in vaccinees had a Th1 phenotype mainly coexpressing IFN-γ and IL-2, whereas patients with active pandemic influenza showed a shift toward cells predominantly expressing IFN-γ. In conclusion, T cells toward seasonal influenza antigens cross-react with pandemic H1N1 antigens and affect induction of specific T cells after pandemic influenza vaccination. In addition, the cytokine patterns of specific T cells during acute H1N1 infection and after vaccination differ, and the predominantly dual-positive cytokine profile of vaccine-induced T cells suggests sufficient functionality to confer successful virus control.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Pandemias/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Imunidade Celular/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Interferon gama/sangue , Interleucina-2/sangue , Pessoa de Meia-Idade , Testes de Neutralização , Estatísticas não ParamétricasRESUMO
SARS-CoV-2 testing is dominated by PCR to guide treatment and individual as well as public health preventive measures. Among 1700 football (soccer) players and staff of the German Bundesliga and Bundesliga 2 who were regularly tested by PCR twice weekly, 98 individuals had a positive PCR (May 2020 to mid-January 2021). A subset of these were retested shortly after the initial positive result. Among those, 11 subjects were identified who only had a transient single positive PCR of low viral load. All individuals were asymptomatic and none developed long COVID. We tested SARS-CoV-2 IgG and IgA as well as SARS-CoV-2 specific CD4 und CD8 positive T cells, and showed that only one out of 11 individuals developed SARS-CoV-2 specific cellular and humoral immunity after the positive PCR, whereas a specific immunity was undetectable in all other individuals. Thus, a single positive PCR might indicate that transient colonization of the upper respiratory tract with SARS-CoV-2 may occur without systemic induction of specific adaptive immunity. Together with test artifacts as another potential reason for a transiently positive test, this finding may favor cautious interpretation of positive PCR results or retesting before initiating intervening treatment or infection control measures in some cases.
RESUMO
BACKGROUND: Individual doses of dual-dose vaccine-regimens are sequentially administered into the deltoid muscle, but little attention has so far been paid to the immunological effects of choosing the ipsilateral or the contralateral side for the second dose. METHODS: In an observational study, 303 previously naive individuals were recruited, who received the second dose of the COVID-19 vaccine BNT162b2 on either the ipsilateral (n = 147) or the contralateral side (n = 156). Spike-specific IgG, IgG-avidity, and neutralizing antibodies were quantified using ELISA and a surrogate assay 2 weeks after dose 2. A subgroup of 143 individuals (64 ipsilateral, 79 contralateral) was analysed for spike-specific CD4 and CD8 T-cells using flow-cytometry. FINDINGS: Median spike-specific IgG-levels did not differ after ipsilateral (4590 (IQR 3438) BAU/ml) or contralateral vaccination (4002 (IQR 3524) BAU/ml, p = 0.106). IgG-avidity was also similar (p = 0.056). However, neutralizing activity was significantly lower after contralateral vaccination (p = 0.024). Likewise, median spike-specific CD8 T-cell levels were significantly lower (p = 0.004). Consequently, the percentage of individuals with detectable CD8 T-cells was significantly lower after contralateral than after ipsilateral vaccination (43.0% versus 67.2%, p = 0.004). Spike specific CD4 T-cell levels were similar in both groups, but showed significantly higher CTLA-4 expression after contralateral vaccination (p = 0.011). These effects were vaccine-specific, as polyclonally stimulated T-cell levels did not differ. INTERPRETATION: Both ipsilateral and contralateral vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming. Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells may have implications for protection from infection and severe disease and support general preference for ipsilateral vaccination. FUNDING: Financial support was provided in part by the State chancellery of the Saarland to M.S.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , Vacina BNT162 , COVID-19/prevenção & controle , Vacinação , Anticorpos Neutralizantes , Imunidade Celular , Imunoglobulina G , Anticorpos AntiviraisRESUMO
Early detection and treatment of syphilis will reduce the infectious period and transmission. We aimed to determine whether screening men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP) for syphilis using Treponema pallidum polymerase chain reaction (PCR) could detect syphilis before the appearance of syphilis antibodies in serology. MSM attending 3-monthly PrEP clinic visits in Melbourne, Australia, were screened with a PCR assay targeting the polA gene of T. pallidum from an anal swab and an oral rinse between November 2019 and March 2020. Participants were serologically screened for syphilis using chemiluminescence immunoassay. A total of 309 asymptomatic participants provided an anal swab and oral rinse sample for T. pallidum PCR screening. Two syphilis cases (0.6%) were detected: one man had a positive serology only; another man had T. pallidum detected by PCR from an anal swab and a positive serology. PCR positivity was 0.3% (n = 1) for anal swabs and 0% (n = 0) for oral rinse. In this study, T. pallidum PCR screening at routine PrEP clinic visits did not identify additional cases of early syphilis over serological screening performed at these visits. IMPORTANCE With the ongoing syphilis epidemic in men who have sex with men (MSM), we investigated the role of using Treponema pallidum polymerase chain reaction (PCR) testing at the oral cavity and anus in MSM taking pre-exposure prophylaxis for the early detection of syphilis. We evaluated whether the PCR tests from these mucosal sites can detect syphilis infection early, before the development of syphilis antibodies in serology. Our study found two syphilis cases among 309 MSM, and only one syphilis case had a positive anal PCR swab, although serology was positive. We conclude that additional PCR testing is likely to be expensive and would not be cost effective for individuals who regularly screen for syphilis. However, future studies with a larger sample size are required.
RESUMO
SARS-CoV-2 infection is associated with an increased rate of thromboembolic events and mortality. Different vaccines are globally used to limit the pandemic. In this report, we present the case of two young female patients with newly diagnosed cerebral sinus vein thrombosis occurring after injection of the vector-based ChAdOx1 vaccine. Both patients presented with unusual headache only. The two of them used an estrogen-containing contraception, had had a history of deep venous thrombosis, and both had MTHFR mutations. Both patients developed SARS-CoV-2 specific humoral and cellular immunity including both CD4 and CD8 T cells. This rare, but serious complication needs to be considered after vaccination of young females, even if there is no evidence of heparin-induced thrombocytopenia.