scholarly journals Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Nick A Kennedy ◽  
Simeng Lin ◽  
James R Goodhand ◽  
Neil Chanchlani ◽  
Nick Powell ◽  
...  
Keyword(s):  
Single Dose ◽  
Primary Outcome ◽  
Geometric Mean ◽  
Antibody Responses ◽  
University Hospital ◽  
Past Infection ◽  
White Ethnicity ◽  
Inflammatory Bowel ◽  
Multivariable Models ◽  
Prior Infection

Background Delayed second-dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single-dose of a SARS-CoV-2 vaccine. Methods Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared to a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin a4B7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations 3-10 weeks after vaccination in patients without evidence of prior infection. Secondary outcomes were seroconversion rates, and antibody responses following past infection or a second dose of the BNT162b2 vaccine. Findings Geometric mean [SD] anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL [5.9] vs 28.8 U/mL [5.4] P<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL [4.9]) vs 13.8 U/mL [5.9] P<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab- compared to vedolizumab-treated patients who received the BNT162b2 (fold change [FC] 0.29 [95% CI 0.21, 0.40], p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 [95% CI 0.30, 0.51], p<0.0001) vaccines. In both models, age > 59 years, immunomodulator use, Crohn's disease, and smoking were associated with lower, whilst non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single-dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. Interpretation Infliximab is associated with attenuated immunogenicity to a single-dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. Funding Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts. Unrestricted educational grants: F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea) and Galapagos NV (Belgium).

scholarly journals Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324789
Author(s):  
Nicholas A Kennedy ◽  
Simeng Lin ◽  
James R Goodhand ◽  
Neil Chanchlani ◽  
Benjamin Hamilton ◽  
...  
Keyword(s):  
Single Dose ◽  
Primary Outcome ◽  
Geometric Mean ◽  
Antibody Responses ◽  
Antibody Assay ◽  
Past Infection ◽  
White Ethnicity ◽  
Registration Number ◽  
Inflammatory Bowel ◽  
Prior Infection

ObjectiveDelayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.DesignAntibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.ResultsGeometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.ConclusionInfliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.Trial registration numberISRCTN45176516.

scholarly journals Measurement of multiple SARS-CoV-2 antibody titer after vaccination represents individual vaccine response and contributes to individually appropriate vaccination schedules

2021 ◽  
Author(s):  
Kenji Ota ◽  
Katsunori Yanagihara ◽  
Satoshi Murakami ◽  
Hiroshi Mukae ◽  
Shigeru Kohno
Keyword(s):  
Single Dose ◽  
Antibody Titer ◽  
Underlying Disease ◽  
Antibody Responses ◽  
Vaccine Response ◽  
Before And After ◽  
Antibody Dynamics ◽  
Prior Infection ◽  
Study Monitoring

<Background> mRNA vaccine (BNT162b2) induces antibodies against Spike protein produced by host cell. However, multiple antibody responses before and after vaccination have not been clarified. <Objective> To clarify multiple antibody responses after mRNA vaccination in a variation of individuals including prior infection of COVID-19. <Methods> This is a prospective, observational study, started from March 15th, 2021. IgG and IgM against Receptor Binding Domain (RBD), and IgG against Nucleocapsid protein (N) were measured by chemiluminescence immunoassay (Alinity, Abbott) in the following schedules; before vaccination, and 7, 14, 28 days, 12, 24, 36, 48 weeks after 1st vaccination. <Results> A total of 136 vaccinees (including 23 of those with prior infection) were enrolled in this analysis. Single-dose vaccination in participants with prior infection yielded higher IgG (RBD) response than two-dose vaccination in participants without prior infection (mean ± standard deviation, 31,523 ± 14,332 arbitrary units [AU] per mL vs. 22,461 ± 15,661 AU/mL, P = 0.01). IgM (RBD) response was observed in participants without prior infection at 14 days after the first vaccination, achieving a comparable antibody titer compared with those with prior infection (1.41 ± 1.93 chemiluminescence of Sample / Calibrator [S/C] vs. 1.96 ± 2.49 S/C, P = 0.24). IgG (N) showed its specificity and usefulness to differentiate those with and without prior infection, regardless of vaccination. We investigated the participants without prior infection to analyze antibody response according to backgrounds. IgG (RBD) response was significantly lower in those ≧ 40 years old than those < 40 years old (19,087 ± 14,630 AU/mL vs. 25,334 ± 15,849 AU/mL, P = 0.04) at 28 days after 1st vaccination. Low antibody responses were observed in vaccinees with underlying disease or immunosuppressive therapy. <Conclusion> Multiple antibody dynamics of vaccinees were clarified in this study. Monitoring each person's antibody titer is warranted in public with expected low and high responders. However, we have yet to observe antibody duration of vaccinees. Therefore, effectiveness of single dose vaccination against those with prior infection is not assessed. Antibody titer follow-up study is in progress.

scholarly journals Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

2021 ◽  
Author(s):  
Jia Wei ◽  
Nicole Stoesser ◽  
Philippa C. Matthews ◽  
Daniel Ayoubkhani ◽  
Ruth Studley ◽  
...  
Keyword(s):  
Single Dose ◽  
Latent Class ◽  
Latent Class Models ◽  
Antibody Responses ◽  
Older Individuals ◽  
The United Kingdom ◽  
Low Responder ◽  
Antibody Levels ◽  
Prior Infection

AbstractWe report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or the BNT162b2 SARS-CoV-2 vaccines, in those who had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after a single dose were lower in older individuals, especially in those aged >60 years. Two vaccine doses achieved high responses across all ages. Antibody levels increased more slowly and to lower levels with a single dose of ChAdOx1 compared with a single dose of BNT162b2, but waned following a single dose of BNT162b2 in older individuals. In descriptive latent class models, we identified four responder subgroups, including a ‘low responder’ group that more commonly consisted of people aged >75 years, males and individuals with long-term health conditions. Given our findings, we propose that available vaccines should be prioritized for those not previously infected and that second doses should be prioritized for individuals aged >60 years. Further data are needed to better understand the extent to which quantitative antibody responses are associated with vaccine-mediated protection.

scholarly journals The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination

2021 ◽  
Author(s):  
Jia Wei ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
Ian Diamond ◽  
Ruth Studley ◽  
...  
Keyword(s):  
Single Dose ◽  
Peak Level ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Population Immunity ◽  
Previous Infection ◽  
Single Vaccination ◽  
Interim Measure ◽  
The Uk ◽  
Prior Infection

AbstractGiven high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single dose of ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults who received at least one vaccination, 13,404 (13.3%) had serological and/or PCR evidence of prior infection. Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations. In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose. Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.

scholarly journals Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

2021 ◽  
Author(s):  
Mohammad Talaei ◽  
Sian Faustini ◽  
Hayley Holt ◽  
David A. Jolliffe ◽  
Giulia Vivaldi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Alcohol Consumption ◽  
Physical Exercise ◽  
Geometric Mean ◽  
Population Based ◽  
International Travel ◽  
Antibody Responses ◽  
White Ethnicity ◽  
Increased Risk

Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults between May 1 and Nov 2, 2020. Information on 88 potential risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. Results: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk included frontline health/care occupation (aOR 1.86, 95% CI 1.49-2.33), international travel (1.22, 1.08-1.37), BMI >30 vs <25 kg/m2 (1.22, 1.05-1.42), Asian/Asian British vs White ethnicity (1.65, 1.10-2.47), and alcohol consumption ≥15 vs 0 units/week (1.26, 1.06-1.49). Light physical exercise associated with decreased risk (0.80, 0.69-0.93, for ≥10 vs 0-4 h/week). Higher titres associated with frontline health/care occupation (aGMR 1.26, 95% CI 1.13-1.41), international travel (1.10, 1.04-1.16), BMI >30 vs <25 kg/m2 (1.09, 1.01-1.17), and Asian/Asian British vs White ethnicity (1.23, 1.03-1.46); these associations were not substantially attenuated by adjustment for disease severity. Conclusions: Higher alcohol consumption and reduced physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, clinical, or behavioural factors investigated.

scholarly journals The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United Kingdom

2021 ◽  
Author(s):  
Jia Wei ◽  
Nicole Stoesser ◽  
Philippa C. Matthews ◽  
Ruth Studley ◽  
Iain Bell ◽  
...  
Keyword(s):  
Single Dose ◽  
General Population ◽  
Older People ◽  
Latent Class ◽  
Latent Class Models ◽  
Antibody Responses ◽  
Older Individuals ◽  
Antibody Levels ◽  
The Impact ◽  
Prior Infection

AbstractReal-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UK’s national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly ‘low responders’. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y. Further data on the relationship between vaccine-mediated protection and antibody responses are needed.

scholarly journals Impact of cardiopulmonary resuscitation on a cannot intubate, cannot oxygenate condition: a randomised crossover simulation research study of the interaction between two algorithms

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e030430
Author(s):  
Thomas Ott ◽  
Jascha Stracke ◽  
Susanna Sellin ◽  
Marc Kriege ◽  
Gerrit Toenges ◽  
...  
Keyword(s):  
Decision Making ◽  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Primary Outcome ◽  
Research Study ◽  
University Hospital ◽  
Simulated Patients ◽  
Stressful Situation ◽  
Simulation Research ◽  
Simulation Centre

ObjectivesDuring a ‘cannot intubate, cannot oxygenate’ situation, asphyxia can lead to cardiac arrest. In this stressful situation, two complex algorithms facilitate decision-making to save a patient’s life: difficult airway management and cardiopulmonary resuscitation. However, the extent to which competition between the two algorithms causes conflicts in the execution of pivotal treatment remains unknown. Due to the rare incidence of this situation and the very low feasibility of such an evaluation in clinical reality, we decided to perform a randomised crossover simulation research study. We propose that even experienced healthcare providers delay cricothyrotomy, a lifesaving approach, due to concurrent cardiopulmonary resuscitation in a ‘cannot intubate, cannot oxygenate’ situation.DesignDue to the rare incidence and dynamics of such a situation, we conducted a randomised crossover simulation research study.SettingWe collected data in our institutional simulation centre between November 2016 and November 2017.ParticipantsWe included 40 experienced staff anaesthesiologists at our tertiary university hospital centre.InterventionThe participants treated two simulated patients, both requiring cricothyrotomy: one patient required cardiopulmonary resuscitation due to asphyxia, and one patient did not require cardiopulmonary resuscitation. Cardiopulmonary resuscitation was the intervention. Participants were evaluated by video records.Primary outcome measuresThe difference in ‘time to ventilation through cricothyrotomy’ between the two situations was the primary outcome measure.ResultsThe results of 40 participants were analysed. No carry-over effects were detected in the crossover design. During cardiopulmonary resuscitation, the median time to ventilation was 22 s (IQR 3–40.5) longer than that without cardiopulmonary resuscitation (p=0.028), including the decision-making time.ConclusionCricothyrotomy, which is the most crucial treatment for cardiac arrest in a ‘cannot intubate, cannot oxygenate’ situation, was delayed by concurrent cardiopulmonary resuscitation. If cardiopulmonary resuscitation delays cricothyrotomy, it should be interrupted to first focus on cricothyrotomy.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial

Diabetologia ◽  
2021 ◽  
Author(s):  
Robin Assfalg ◽  
Jan Knoop ◽  
Kristi L. Hoffman ◽  
Markus Pfirrmann ◽  
Jose Maria Zapardiel-Gonzalo ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Antibody Responses ◽  
Oral Insulin ◽  
Cell Responses ◽  
Randomised Controlled

Abstract Aims/hypothesis Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome. Methods A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory. Results Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes. Conclusions/interpretation The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells. Trial registration Clinicaltrials.gov NCT02547519 Funding The main funding source was the German Center for Diabetes Research (DZD e.V.) Graphical abstract

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