scholarly journals Immunogenicity of The BNT162b2 mRNA COVID-19 Vaccine in Patients With Primary Brain Tumors: A Prospective Cohort Study

Author(s):  
Amir Massarweh ◽  
Roi Tschernichovsky ◽  
Amos Stemmer ◽  
Alexandra Benouaich-Amiel ◽  
Tali Siegal ◽  
...  

Abstract Purpose Immunogenicity of Covid-19 vaccines may be negatively impacted by anti-cancer treatment. The management of primary brain tumor (PBT) patients routinely includes temozolomide and steroids, which are immune-suppressive. In this study, we aimed to determine the rate of seropositivity in PBT patients following receipt of two doses of the BNT162b2 vaccine. Methods We prospectively evaluated IgG antibody levels against SARS-CoV-2 spike protein in 17 PBT patients following two doses of the BNT162b2 mRNA vaccine. IgG levels were collected at two time points: T1 - after a median of 44 days from the second vaccine dose and T2 - after a median of 130 days from the second dose. Titers were compared against a group of healthy controls (HC) comprised of patients’ family members/caregivers. Results At T1, 88.2% (15/17) of PBT patients achieved seroconversion, compared with 100% (12/12) of HCs. Median IgG titer was significantly lower in the PBT group compared to the HC group (1,908 AU/mL vs 8,198 AU/mL, respectively; p=0.002). At T2, 80% (12/15) of PBT achieved seroconversion, compared to 100% (10/10) of the HCs. Median IgG titer remained significantly lower in the PBT group (410 vs 1687; p=0.002). All three PBT patients who failed to seroconvert at T2 had been treated with corticosteroids during vaccination. In a univariate analysis, steroid use was negatively associated with antibody titer. Conclusion Most PBT patients achieve seroconversion after receiving the BNT162b2 vaccine, but with lower IgG titer compared to HCs. Steroid use during the vaccination period is associated with lower titer.

2021 ◽  
pp. annrheumdis-2021-220647
Author(s):  
Victoria Furer ◽  
Tali Eviatar ◽  
Devy Zisman ◽  
Hagit Peleg ◽  
Daphna Paran ◽  
...  

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.ConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.


Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 325
Author(s):  
Marco Krasselt ◽  
Christoph Baerwald ◽  
Uwe G. Liebert ◽  
Olga Seifert

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4871-4871
Author(s):  
Francesco Saraceni ◽  
Alessandro Fiorentini ◽  
Sonia Morè ◽  
Selene Guerzoni ◽  
Bruna Puglisi ◽  
...  

Abstract Recipients of allogeneic hematopoietic stem cell transplant (HSCT) have been excluded from clinical trials of SARS-CoV-2 messenger RNA (mRNA) vaccines; however, since these patients are at higher risk of severe complications following infection, they have been given high priority in vaccination campaigns worldwide. In this prospective observational study, we evaluated the immunogenicity of two BNT162b2 (Pfizer-BioNTech) vaccine doses in allogeneic HSCT recipients compared to healthy controls. IgG antibodies to the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 were analyzed by SARS-CoV-2 IgG II Quant (Abbott, Ireland). The cutoff value of the test used in this study is 7.1 BAU/mL (Binding Antibody Unit/mL) and the results greater than 7.1 indicate that seroconversion has occurred, as recommended by the manufacturer. Peripheral blood samples were collected for immunological analysis at three timepoints: pre-vaccine baseline (w0, before the first BNT162b2 dose), week 3 (w3, before the second vaccine dose) and week 5 (w5, 2 weeks following the second dose). Patients older than 18 years who received BNT162b2 vaccine following an HSCT at seven Italian centers were included in the study. Enrolled patients received two successive doses (at 3-week interval) at a median of 15 months (range 2-141) after HSCT. Twenty-nine age-matched health care workers who were vaccinated with BNT162b2 were recruited as the control group. Among the 34 patients evaluable for serological response, three patients were excluded from the analysis as the baseline serology demonstrated previous natural SARS-CoV-2 infection. On w3, after the first vaccine dose 7/31 (23%) patients developed anti-S IgG antibodies as compared to 28/29 (97%) controls (p&lt;0.01). HSCT recipients showed lower antibody titers (median 1.8 BAU, range 0-481) as compared to healthy controls (median 118 BAU, range 6-1172, p&lt;0.01). In univariate analysis, transplant-to-vaccination interval (&gt;12 months, p&lt;0.01), baseline CD4+ T cell count (&gt;200/mm3, p=0.01), and CD4+CD45RA+ T naive cell count (&gt;100/ mm3, p&lt;0.01) were significantly associated with antibody response after the first vaccine dose. On w5, after the second vaccine dose, 24/31 (77%) of the patients showed antibody response, as compared to 99% of healthy controls (p&lt;0.01); in fact, 71% of non-responders to the first dose developed IgG antibodies after vaccine boost (Figure 1). Median antibody titer after second dose was 350 BAU/ml (0-21.731). In univariate analysis, no significant association was found between patient characteristics and immunogenicity after vaccine boost. Adverse events were rare and modest. Nine percent of the patients reported mild local reactions after vaccine administration, including pain at the injection site and less commonly local erythema, local lymphadenopathy, or swelling; 35% of patients reported systemic adverse events, and all were mild. The most frequently reported systemic reactions included weakness (15%), headache (9%), and diarrhea (3%). In conclusion, in recipients of HSCT, a single dose of the BNT162b2 SARS-CoV-2 vaccine yielded poor efficacy, while immunogenicity increased significantly after vaccine boost at day 21 after the first dose. Patients who received vaccines beyond one year after transplant were more likely to mount anti-S IgG antibodies, which could be due to a broader immune reconstitution, as we observed an enhanced response to single BNT162b2 vaccine dose in patients with higher CD4+ T cell and particularly CD4+CD45RA+ naïve T cell counts. Figure 1 Figure 1. Disclosures Kordasti: Alexion: Honoraria; Celgene: Research Funding; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy.


2021 ◽  
Vol 15 (10) ◽  
pp. e0009732
Author(s):  
Yoanne D. Mouwenda ◽  
Madeleine E. Betouke Ongwe ◽  
Friederike Sonnet ◽  
Koen A. Stam ◽  
Lucja A. Labuda ◽  
...  

Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1. In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity.


2021 ◽  
Author(s):  
Joseph E. Ebinger ◽  
Justyna Fert-Bober ◽  
Ignat Printsev ◽  
Min Wu ◽  
Nancy Sun ◽  
...  

AbstractIn a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1578.2-1578
Author(s):  
N. Gokcen ◽  
A. Komac ◽  
F. Tuncer ◽  
A. Yazici ◽  
A. Cefle

Background:Sleep disturbances have been described in Systemic Sclerosis (SSc). Confounding factors related to sleep quality are also investigated. Although sleep hygiene plays an important role in sleep quality, as far as we know, there are not enough data to show the effect of sleep hygiene on sleep quality of SSc.Objectives:To investigate sleep hygiene, its impact on sleep quality, and its association with demographic-clinical factors in patients with SSc, rheumatoid arthritis (RA), and healthy controls.Methods:The study was designed as cross-sectional. Forty-nine patients with SSc who fulfilled the 2013 ACR/EULAR classification criteria for SSc, 66 patients with RA who fulfilled 1987 revised classification criteria, and 30 healthy controls were included in the study. All participants were female. Demographic and clinical variables were documented. Disease activity index of both SSc and RA was calculated. SSc patients were assessed by questionnaires including Short Form 36 (SF-36), The Health Assessment Questionnaire Disability Index (HAQ-DI), Beck Anxiety and Beck Depression Inventory, Pittsburg Sleep Quality Index (PSQI), Sleep Hygiene Index (SHI). Additionally, RA patients and healthy controls were estimated by HAQ-DI, Beck Anxiety and Beck Depression Inventory, PSQI, and SHI. Logistic regression analysis was used to determine the predictors of sleep quality.Results:Preliminary results of the study were given. The baseline demographics were similar among groups. When comparing groups according to HAQ-DI, Beck Anxiety and Beck Depression Inventory, PSQI, and SHI, we found higher scores in SSc and RA rather than healthy controls (p<0.001, p=0.001, p=0.001, p<0.001, p=0.003; respectively). While depression and sleep hygiene were determined as the risk factors of sleep quality in SSc in univariate analysis, depression (OR=1.380, 95%CI: 1.065−1.784, p=0.015) and sleep hygiene (OR=1.201, 95%CI: 1.003−1.439, p=0.046) were also found in multivariate logistic model. In RA patients, while health status, depression, and anxiety were found as risk factors according to the univariate analysis, depression (OR=1.120, 95%CI: 1.006−1.245, p=0.038) was the only factor according to multivariate logistic model (Table).Conclusion:Although depression is a well-known clinical variable impacting on sleep quality, sleep hygiene should also be kept in mind as a confounding factor.References:[1]Milette K, Hudson M, Körner A, et al. Sleep disturbances in systemic sclerosis: evidence for the role of gastrointestinal symptoms, pain and pruritus. Rheumatology (Oxford). 2013 Sep;52(9):1715-20.[2]Sariyildiz MA, Batmaz I, Budulgan M, et al. Sleep quality in patients with systemic sclerosis: relationship between the clinical variables, depressive symptoms, functional status, and the quality of life. Rheumatol Int. 2013 Aug;33(8):1973-9.TableUnivariate logistic regression analysis of clinical variables to assess predictors of sleep qualitySystemic sclerosisRheumatoid arthritisOR (95% CI)pOR (95% CI)pHAQ-DI1.019 (0.882−1.177)0.8011.089 (1.011−1.173)0.025BDI score1.293 (1.082−1.547)0.0051.129 (1.036−1.230)0.006BAI score1.080 (0.997−1.169)0.0591.122 (1.038−1.214)0.004SHI1.200 (1.060−1.357)0.0041.048 (0.965−1.137)0.264Disease activitya0.707 (0.439−1.138)0.1531.446 (0.839−2.492)0.185aDisease activity was calculated by Valentini disease activity index for SSc and DAS28-CRP for RA.Disclosure of Interests:None declared


2020 ◽  
Vol 8 (9) ◽  
pp. 1287
Author(s):  
Minna M. Hankaniemi ◽  
Mo A. Baikoghli ◽  
Virginia M. Stone ◽  
Li Xing ◽  
Outi Väätäinen ◽  
...  

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Lind ◽  
Ilaria Marzinotto ◽  
Cristina Brigatti ◽  
Anita Ramelius ◽  
Lorenzo Piemonti ◽  
...  

AbstractAn increased incidence of narcolepsy type 1 (NT1) was observed in Scandinavia following the 2009–2010 influenza Pandemrix vaccination. The association between NT1 and HLA-DQB1*06:02:01 supported the view of the vaccine as an etiological agent. A/H1N1 hemagglutinin (HA) is the main antigenic determinant of the host neutralization antibody response. Using two different immunoassays, the Luciferase Immunoprecipitation System (LIPS) and Radiobinding Assay (RBA), we investigated HA antibody levels and affinity in an exploratory and in a confirmatory cohort of Swedish NT1 patients and healthy controls vaccinated with Pandemrix. HA antibodies were increased in NT1 patients compared to controls in the exploratory (LIPS p = 0.0295, RBA p = 0.0369) but not in the confirmatory cohort (LIPS p = 0.55, RBA p = 0.625). HA antibody affinity, assessed by competition with Pandemrix vaccine, was comparable between patients and controls (LIPS: 48 vs. 39 ng/ml, p = 0.81; RBA: 472 vs. 491 ng/ml, p = 0.65). The LIPS assay also detected higher HA antibody titres as associated with HLA-DQB1*06:02:01 (p = 0.02). Our study shows that following Pandemrix vaccination, HA antibodies levels and affinity were comparable NT1 patients and controls and suggests that HA antibodies are unlikely to play a role in NT1 pathogenesis.


2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmut Alpayci ◽  
Aysel Milanlioglu ◽  
Veysel Delen ◽  
Mehmet Nuri Aydin ◽  
Huseyin Guducuoglu ◽  
...  

Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS). Anticyclic citrullinated peptide (anti-CCP) antibody is used in the early diagnosis of rheumatoid arthritis (RA). The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years), 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years), and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years) were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA). The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls(P<0.001). Moreover, anti-CCP antibody was positive in 43 (83%) patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores(r=-0.250). In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.


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