BACKGROUND: Cancer patients are particularly vulnerable during the COVID-19 pandemic. Vaccinations are essential in controlling the pandemic. However, due to their exclusion from clinical trials for COVID-19 vaccines, there is limited data on the vaccines' effectiveness and safety for this group. OBJECTIVES: We evaluated humoral (anti-S antibody) and cellular (T-cell) immune response in patients with solid cancer on systemic anticancer treatment versus healthy controls prime-vaccinated by the BNT162b2 COVID-19 mRNA vaccine. METHODS: CoVigi was the phase IV prospective open-label non-randomized multicentric clinical trial evaluating anti-S and anti-N SARS-CoV-2 antibodies and SARS-CoV-2-specific T-cell response by IFN-γ-release assay in several time points during the prime COVID-19 mRNA vaccination (prior to the first vaccine dose, prior to the second dose, at 4-8 weeks, at 3 months, and 6 months after vaccination). Immune response was analyzed in the context of previous SARS-CoV-2 infection and anticancer therapy (chemotherapy (CT) + monoclonal antibodies (mAb), mAb, immune checkpoint inhibitors, tyrosine kinase inhibitors, and curative radiotherapy). RESULTS: Among 204 patients with solid cancer and 73 healthy controls, 65% of SARS-CoV-2-naïve patients with cancer developed anti-S antibodies after the first vaccine dose, rising to 92% after the second dose. By 6 months, all BNT162b2-vaccinated patients with solid cancer developed antibody response. Patients treated with CT showed impaired both humoral and cellular immune response to BNT162b2 vaccination. Antibody levels in SARS-CoV-2-recovered patients were comparable to healthy controls. T-cell response peaked after the second dose of BNT162b2 and was not significantly impaired in solid cancer patients except those treated with CT. CONCLUSION: Immune response to BNT162b2 COVID-19 mRNA vaccine is substantially shaped by pre-vaccination COVID-19 infection. All patients with solid cancer on active anticancer therapy exhibited seroconversion after COVID-19 vaccination, although the extent of both humoral and cell immune response was substantially hampered in those treated by CT. TRIAL REGISTRATION: EudraCT No. 2021-000566-14 (registration date February 17, 2021).
- Publication type
- Journal Article MeSH
Cíl: Observační studie sledující dynamiku tvorby protilátek IgG proti S proteinu SARS-CoV-2 u osob očkovaných dvěma dávkami mRNA vakcíny Pfizer-BioNTech BNT162b2 (Comirnaty) byla provedena v období let 2021–2022 u skupiny dobrovolníků bez známek předcházející nákazy SARS-CoV-2 a u skupiny s anamnézou přirozené infekce covidem-19. Hlavním cílem bylo monitorovat hladiny protilátek až do 12 měsíců po druhé dávce a zjistit podíl očkovaných, u kterých došlo k sérokonverzi. Studie také hodnotila případy selhání vakcíny v rámci třinácti měsíců po očkování. Metodika: Před zahájením očkování byly u účastníků studie provedeny laboratorní testy na protilátky IgG proti S proteinu SARS-CoV-2 a shromážděna anamnestická data týkající se onemocnění covidem-19. Na základě negativních výsledků byla vytvořena kohorta imunologicky naivních osob, které byly následně očkovány dvěma dávkami vakcíny BNT162b2 (Comirnaty). Vzorky venózní krve byly odebírány v šesti časových bodech: před první dávkou, dva až tři týdny po první dávce, měsíc po druhé dávce, tři až čtyři měsíce po druhé dávce, půl roku a jeden rok po druhé dávce. Doplňkovou kohortu tvořili dobrovolníci s pozitivním nálezem protilátek nebo potvrzeným onemocněním covidem-19. U části z nich byla rovněž sledována dynamika vývoje protilátek po očkování. Účastníci měsíčně vyplňovali dotazníky o symptomech respiračních infekcí, zaměřené na detekci selhání vakcíny. Výsledky: Studie zahrnula 166 účastníků, kteří před očkováním neměli protilátky proti S proteinu SARS-CoV-2. Medián věku byl 52 let, převažovaly ženy (71,1 %). Po první a druhé dávce vakcíny hladiny protilátek vykázaly významný vzestup, poté následoval postupný pokles. U všech účastníků, kromě jednoho imunosuprimovaného, proběhla sérokonverze. Podíl selhání vakcíny proti onemocnění covidem-19 do 12 měsíců byl 13,3 %. Druhá kohorta zahrnula 60 účastníků s předchozí infekcí SARS-CoV-2. Po očkování došlo u této skupiny k výraznému nárůstu hladin protilátek, který byl vyšší než u osob bez předchozí infekce. Druhá dávka u těchto osob již nezvýšila hladiny protilátek statisticky významně. Závěry: Studie potvrdila, že očkování mRNA vakcínou BNT162b2 vyvolává silnou protilátkovou odpověď, s většinovou sérokonverzí již po první dávce. Starší osoby vykazovaly nižší protilátkovou odpověď, což zdůrazňuje význam posilujících dávek. U osob s prožitou infekcí SARS-CoV-2 byly po první dávce vakcíny protilátky výrazně vyšší než u naivních jedinců. Výsledky přispívají k porozumění dynamiky protilátkové odpovědi a naznačují potřebu dalšího výzkumu zaměřeného na optimalizaci očkovacích schémat.
Objective: An observational study was conducted from 2021 to 2022 to track the dynamics of the production of IgG antibody against the SARS-CoV-2 S protein in individuals vaccinated with two doses of the Pfizer-BioNTech mRNA vaccine BNT162b2 (Comirnaty). The study included a group of volunteers without any previous signs of SARS-CoV-2 infection as well as a group with a history of natural COVID-19 infection. The primary objective was to monitor antibody levels up to 12 months after the second dose and determine the proportion of vaccinated individuals who underwent seroconversion. The study also evaluated cases of vaccine failure within 13 months post-vaccination. Methods: Before the vaccination began, participants had laboratory tests for IgG antibodies against the SARS-CoV-2 S protein, and their medical history related to COVID-19 was taken. Based on negative test results, a cohort of immunologically na?ve individuals was formed and subsequently vaccinated with two doses of BNT162b2 (Comirnaty). Venous blood samples were collected at six time points: before the first dose, 2–3 weeks after the first dose, one month after the second dose, 3–4 months after the second dose, 6 months after the second dose, and 12 months after the second dose. A supplementary cohort included volunteers with positive antibody findings or confirmed COVID-19 infection. In some of these individuals, the dynamics of post-vaccination antibody response was also monitored. Participants filled out monthly questionnaires about respiratory infection symptoms to detect vaccine failure. Results: The study included 166 participants who did not have SARS-CoV-2 S protein antibodies prior to vaccination. The median age was 52 years, with a higher proportion of women (71.1%). After the first and second doses of the vaccine, antibody levels showed a significant increase, followed by a gradual decline over 12 months. Seroconversion occurred in all participants except for one immunosuppressed individual. The vaccine failure rate against COVID-19 within 12 months was 13.3%. The second cohort included 60 participants with prior SARS-CoV-2 infection. In this group, post-vaccination antibody levels increased significantly, more than in individuals without prior infection. The second dose did not result in further statistically significant increase in antibody levels for this cohort. Conclusions: The study confirmed that the BNT162b2 mRNA vaccine induces a strong antibody response, with the majority of participants experiencing seroconversion after the first dose. Older individuals exhibited a lower antibody response, highlighting the importance of booster doses. In individuals with prior SARS-CoV-2 infection, antibody levels were significantly higher after the first vaccine dose than in na?ve individuals. These findings add to understanding antibody response dynamics and suggest the need for further research focused on optimizing vaccination schedules.
Tick-borne encephalitis virus (TBEV) infection can manifest as disease of variable severity, ranging from subclinical infection to severe disease with neurological involvement and potentially fatal outcome. Although TBE is recognized as a major public health problem in Europe, the true burden of disease is potentially underestimated. Here, we investigated TBEV-specific antibody prevalence, infection incidence, and seroreversion and antibody decline rates in a prospective Swiss healthcare worker (HCW) cohort. We screened serum samples from 1444 HCWs between June and October 2020, and from a subset again between August and September 2021, using a TBEV envelope (E) protein IgG ELISA. Positive samples underwent further analysis with a TBEV non-structural protein 1 (NS1) IgG ELISA, and seroconversions in unvaccinated individuals were confirmed by seroneutralization testing. Questionnaire data were used to determine vaccination status and risk factors. TBEV E protein-specific IgG prevalence was 72.1% (95% CI 68.2-75.7%) in TBEV-vaccinated and 6% (95% CI 4.4-7.8%) in unvaccinated individuals. The estimated annual incidence of infection was 735/100,000. Age was the only factor significantly associated with seroprevalence. The seroreversion rate in unvaccinated individuals was 30.3% within one year, which is almost ten times higher than in vaccinated individuals (3.4%, annual decline rate 8.0%). NS1-specific IgG antibodies were six times more common in vaccinated than unvaccinated HCWs. In conclusion, undetected TBEV infections are common, and infection incidence is much higher than reported clinical cases. Individuals with abortive infections have high antibody decline and seroreversion rates. Whether lifelong protection is conferred and by which immune subsets remain unclear.
- MeSH
- Adult MeSH
- Immunoglobulin G blood MeSH
- Incidence MeSH
- Encephalitis, Tick-Borne * epidemiology immunology blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Antibodies, Viral * blood MeSH
- Aged MeSH
- Seroepidemiologic Studies MeSH
- Encephalitis Viruses, Tick-Borne * immunology MeSH
- Health Personnel statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Switzerland MeSH
Vaccines represent an essential tool for the prevention of infectious diseases. Upon administration, a complex interaction occurs between the vaccine formulation and the recipient's immune system, ultimately resulting in protection against disease. Significant variability exists in individual and population responses to vaccination, and these differences remain the focus of the ongoing research. Notably, well-documented factors, such as age, gender, and genetic predisposition, influence immune responses. In contrast, the effects of overweight and obesity have not been as thoroughly investigated. The evidence indicates that a high body mass index (BMI) constitutes a significant risk factor for infections in general, with adipose tissue playing a crucial role in modulating the immune response. Furthermore, suboptimal levels of vaccine seroconversion have been observed among individuals with obesity. This review provides a plausible examination of the immunity and protection conferred by various vaccines in individuals with an overweight status, offering a comprehensive analysis of the mechanisms to enhance vaccination efficiency.
- MeSH
- Body Mass Index MeSH
- Humans MeSH
- Obesity * immunology MeSH
- Sex Factors MeSH
- Adipose Tissue * immunology metabolism MeSH
- Vaccination MeSH
- Vaccines * immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.
- MeSH
- COVID-19 * MeSH
- Adult MeSH
- Hematologic Neoplasms * complications drug therapy epidemiology MeSH
- Humans MeSH
- Antibodies, Monoclonal MeSH
- Pre-Exposure Prophylaxis * MeSH
- Retrospective Studies MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Czech Republic MeSH
Measuring T cell response can add information about antivirus immunity provided by antibody test results. The study evaluates the impact of a third mRNA COVID-19 vaccine dose on T cell response and antibody production in kidney transplant recipients (25 KTRs) versus healthy controls (26 Hc). Results show a significant rise in S-activated CD4+CD154+IFN?+TNF?+ double producer cells in both KTRs (p=0.025) and Hc (p=0.009) as well as increased spike antibody response in KTRs (p=0.00019) and Hc (p=3.10-8) third-month post-third dose. Moreover, the study revealed a drop in seronegative KTRs (non-responders) from 9/25 (36%) pre-third dose to 2/25 (7%) at 3 months post-third dose while 5/9 (56%) of non-responders post-second dose showed specific T cell responses. Notably, the third dose significantly improved seroconversion rates in both KTRs and Hc, although Hc individuals exhibited higher antibody levels. Key words: mRNA COVID-19 vaccine, T cells, SARS-CoV-2 antibodies, Kidney transplantation, mRNA vaccination.
- MeSH
- COVID-19 * immunology prevention & control MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Viral blood MeSH
- SARS-CoV-2 immunology MeSH
- Aged MeSH
- T-Lymphocytes * immunology MeSH
- Kidney Transplantation * adverse effects MeSH
- Vaccination methods MeSH
- COVID-19 Vaccines * immunology administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Předvakcinační a povakcinační vyšetření protilátek proti kmenům obsažených ve vakcínách pro sezónu 2023/2024 bylo zajištěno u 80 pacientů dialyzačních středisek. Hodnocení registrovaných vakcín potvrdilo jejich význam při prevenci chřipky u dialyzovaných.
Pre-vaccination and post-vaccination screening of antibodies against the strains included in the 2023/2024 vaccines was conducted in 80 dialysis patients. The evaluation of the authorized vaccines confirmed their significant role in the prevention of influenza.
BACKGROUND: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. METHODS: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. RESULTS: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. CONCLUSIONS: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
- Publication type
- Journal Article 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
- Kidney Failure, Chronic surgery immunology MeSH
- Circadian Rhythm immunology MeSH
- COVID-19 * prevention & control immunology MeSH
- Adult MeSH
- Immunity, Humoral * MeSH
- Immunoglobulin G blood immunology MeSH
- Immunosuppressive Agents administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Transplant Recipients MeSH
- Antibodies, Viral * blood immunology MeSH
- Graft Rejection immunology prevention & control MeSH
- SARS-CoV-2 * immunology MeSH
- Aged MeSH
- Kidney Transplantation * MeSH
- Vaccination MeSH
- COVID-19 Vaccines * immunology administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.
- MeSH
- Immunity, Cellular MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * drug therapy MeSH
- COVID-19 * MeSH
- Humans MeSH
- Antibodies, Viral MeSH
- Antibodies MeSH
- Interleukin-2 Receptor alpha Subunit MeSH
- SARS-CoV-2 MeSH
- Vaccination MeSH
- COVID-19 Vaccines MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
