Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * krev imunologie MeSH
- příjemce transplantátu * MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 imunologie aplikace a dávkování MeSH
- vakcíny proti COVID-19 imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. OBJECTIVES: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. METHODS: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. RESULTS: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. CONCLUSION: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.
- MeSH
- B-lymfocyty imunologie MeSH
- buněčná imunita imunologie MeSH
- COVID-19 * imunologie MeSH
- dospělí MeSH
- ELISPOT MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- imunologická paměť MeSH
- leukocyty mononukleární imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- T-lymfocyty imunologie MeSH
- vakcíny proti COVID-19 imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Although severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid (SARS-CoV-2 mRNA) vaccines are effective in kidney transplant recipients (KTRs), their immune response to vaccination is blunted by immunosuppression. Other tools enhancing vaccination response are therefore needed. Interestingly, aligning vaccine administration with circadian rhythms (chronovaccination) has been shown to boost immune response. However, its applicability in KTRs, whose circadian rhythms are likely disrupted by immunosuppressants, remains unclear. To assess the impact of vaccination timing on seroconversion in the KTRs population, we analyzed data from 553 virus-naïve KTRs who received 2 doses of messenger ribonucleic acid (mRNA) vaccine. Bayesian logistic regression was employed, adjusting for previously identified predictors of seroconversion, including allograft function, maintenance immunosuppressants, or time since transplantation. SARS-CoV-2 immunoglobulin G (IgG) levels were measured with a median of 47 days after the second dose. The results did not reveal a reliable effect of timing of the first dose but did indicate that earlier timing for the second dose brings a notable benefit-every 1-hour delay in the application was associated with a 16% reduction in the odds of seroconversion (OR 0.84, 95% CI 0.71, 0.998). Similar results were obtained from quantile regression modeling IgG levels. In conclusion, morning vaccination is emerging as a promising and easily implementable strategy to enhance vaccine response in KTRs.
- MeSH
- chronické selhání ledvin chirurgie imunologie MeSH
- cirkadiánní rytmus imunologie MeSH
- COVID-19 * prevence a kontrola imunologie MeSH
- dospělí MeSH
- humorální imunita * MeSH
- imunoglobulin G krev imunologie MeSH
- imunosupresiva aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- příjemce transplantátu MeSH
- protilátky virové * krev imunologie MeSH
- rejekce štěpu imunologie prevence a kontrola MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Diabetes mellitus 1. typu je důsledek autoimunitní inzulitidy, která je podstatně více heterogenní než se dříve předpokládalo. histopatologické nálezy se u autoimunitní inzulitidy liší podle věku jedince, což odráží i patogenetickou heterogenitu onemocnění. tato heterogenita může ovlivnit i imunointervenční strategie a s tímto ohledem začaly být popisovány specifické endotypy choroby. Průlomovým krokem v sekundární prevenci propuknutí diabetu 1. typu bylo v roce 2022 schválení teplizumabu (monoklonální protilátka proti znaku cD3) ve Spojených státech jako prvního tzv. chorobu modifikujícího léku pro osoby ve ii. stadiu rozvoje diabetu (toto stadium je charakterizované přítomností dvou a více autoprotilátek a prediabetickou dysglykemií). teplizumab účinně oddaluje progresi onemocnění do stadia klinického diabetu v průměru asi o dva roky. tento fakt podporuje rozvoj celopopulačních screeningových programů, které mají za cíl pomocí vyšetřování autoprotilátek (podle stanoveného genetického rizika nebo i bez něj) vytipovat jedince vhodné pro aplikaci různých preventivních opatření.
Type 1 diabetes mellitus is consequence of autoimmune insulitis which is significantly more heterogeneous than previously thought. histopathological findings in autoimmune insulitis differ according to the age of the individual, which also reflects the pathogenetic heterogeneity of the disease. immune intervention strategies should be adapted to this heterogeneity. With this in mind, specific endotypes of the disease have begun to be described. a breakthrough step was the approval of teplizumab (a monoclonal anti-cD3 antibody) in the United States in 2022 as the first so-called disease-modifying drug for people in ii. stage of diabetes development (this stage is characterized by the presence of two or more autoantibodies and prediabetic dysglycemia). teplizumab effectively delays progression to clinical diabetes by about two years on average. this fact stimulates the development of population-wide screening programs that, with the help of autoantibody testing (according to the determination of genetic risk or separately), aim to select individuals suitable for the application of various preventive measures.
- Klíčová slova
- autoimunitní inzulitida,
- MeSH
- diabetes mellitus 1. typu * imunologie patofyziologie MeSH
- humorální imunita MeSH
- lidé MeSH
- střevní mikroflóra MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.
- MeSH
- buněčná imunita MeSH
- chronická lymfatická leukemie * farmakoterapie MeSH
- COVID-19 * prevence a kontrola etiologie MeSH
- humorální imunita MeSH
- lidé MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- rituximab terapeutické užití MeSH
- SARS-CoV-2 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Nemocní po transplantaci ledviny jsou ve vyšším riziku závažných projevů nemoci covid-19. Po prodělání nemoci byla u nemocných po transplantaci ledviny popsána solidní míra sérokonverze (vytvoření specifických protilátek). Imunosupresivní terapie, především mykofenolová kyselina, limituje schopnost vytvoření specifických protilátek nebo specifických T – lymfocytů jako odpověď na očkování doporučenými mRNA vakcínami. Posilující třetí dávka mRNA vakcíny dále zvyšuje šanci na sérokonverzi bez ohledu na zvolený typ vakcíny. Očkování po proběhlém onemocnění vede k vytvoření protilátek ve vysokém titru u většiny nemocných. Vyšetření humorální nebo celulární imunity je ale jenom pomocným nástrojem k posouzení specifické imunokompetence u nemocných léčených imunosupresí.
Kidney transplant recipients are at high risk of severe covid-19. Seroconversion rates comparable to those of the general population were previously described after the natural course of the disease in kidney transplant recipients. Immunosuppressive therapy, such as mycophenolic acid, limits the production of specific T-cells and antibodies following mRNA vaccination. A third booster dose significantly improves the humoral response regardless of the vaccine type chosen. Furthermore, vaccination following covid-19 infection results in high levels of specific antibodies in the majority of patients. However, the testing of humoral or cellular immune response in kidney transplant recipients is only an auxiliary tool in assessing their immunocompetence.
OBJECTIVES: The study was aimed at the characterization of humoral immunity in acute SARS-CoV-2 infection. BACKGROUND: Humoral immunity plays a central role in the protection from infection due to SARS-CoV-2, causative agent of coronavirus diseases 2019 (COVID-19). PATIENTS AND METHODS: In 24 adult patients hospitalized with COVID-19, the functional subsets of circulating B-lymphocytes and SARS-CoV-2 specific IgA and IgG antibodies were analyzed using a flow cytometry and immunoassays, respectively. RESULTS: Circulating plasmablasts and memory B-lymphocytes were significantly elevated and regulatory B-lymphocytes significantly decreased in the patients in comparison with 11 age- and sex-matched SARS-CoV-2 seronegative healthy adults. Next, circulating plasmablasts correlated negatively with the levels of SARS-CoV-2 specific IgG antibodies, which were detectable in 9 out of 15 tested patients. In addition, SARS-CoV-2 specific IgA antibodies were detectable in 13 of 15 tested patients and did not demonstrate correlation with any B-lymphocyte subset. CONCLUSION: Severe course of COVID-19 is associated with significant changes of phenotypes of circulating B-lymphocytes and elevated circulating plasmablasts correlate with decreased SARS-CoV-2-specific IgG antibodies (Tab. 2, Fig. 3, Ref. 14).
- MeSH
- B-lymfocyty MeSH
- COVID-19 * imunologie krev MeSH
- dospělí MeSH
- humorální imunita MeSH
- imunoglobulinové izotypy imunologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- plazmatické buňky * MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: Knowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease [IBD] patients is limited. Therefore, SARS-CoV-2-specific T-cell responses and antibodies were analysed in 60 IBD vaccine recipients and 30 controls. METHODS: SARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. A SARS-CoV-2 interferon-gamma released assay [IGRA] was performed in all vaccinees at week 26. RESULTS: At weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 [18%] vaccinated individuals had a negative IGRA test result, seven of 90 [8%] were borderline and 67 [74%] had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However, the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinated individuals with low or borderline IGRA, treatment with tumour necrosis factor-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient. CONCLUSIONS: Simple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- humorální imunita MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- imunoglobulin G MeSH
- interferon gama MeSH
- lidé MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- virové vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Coronavirus disease 2019 (COVID-19) vaccines effectively elicit humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthy populations. This immunity decreases several months after vaccination. However, the efficacy of vaccine-induced immunity and its durability in patients with severe asthma on biological therapy are unknown. In this study, we evaluated the effectiveness and durability of mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy. The study included 34 patients with severe asthma treated with anti-IgE (omalizumab, n=17), anti-IL5 (mepolizumab, n=13; reslizumab, n=3), or anti-IL5R (benralizumab, n=1) biological therapy. All patients were vaccinated with two doses of the BNT162b2 mRNA vaccine with a 6-week interval between the doses. We found that this COVID-19 vaccination regimen elicited SARS-CoV-2-specific humoral and cellular immunity, which had significantly declined 6 months after receipt of the second dose of the vaccine. The type of biological treatment did not affect vaccine-elicited immunity. However, patient age negatively impacted the vaccine-induced humoral response. On the other hand, no such age-related impact on vaccine-elicited cellular immunity was observed. Our findings show that treatment of patients with severe asthma with biological therapy does not compromise the effectiveness or durability of COVID-19 vaccine-induced immunity.
- MeSH
- bronchiální astma * terapie MeSH
- buněčná imunita MeSH
- COVID-19 * prevence a kontrola MeSH
- humorální imunita MeSH
- lidé MeSH
- mRNA vakcíny MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- syntetické vakcíny MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
