scholarly journals Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators.

Author(s):  
Esteban Rodriguez-Marrtino ◽  
Rafael Medina-Prieto ◽  
Jorge Santana-Bagur ◽  
Maria Sante ◽  
Petraleigh Pantoja ◽  
...  

Patients with immune conditions and immune-modifying therapies were excluded from the Covid-19 vaccine trials. Studies have shown conflicting response to different vaccines in persons receiving immune suppressors or biologics. The aim of this study is to evaluate humoral and cellular response to Covid-19 vaccines in patients with Inflammatory Bowel Disease (IBD) using biologic and/or immunomodulatory (IMM) therapies. Methods: Participants are adults with IBD receiving biologics or IMM planning to receive a Covid 19 vaccine. Cellular immunity (CD4+ and CD8+ T cell levels) with flow cytometry are measured at baseline and 2 weeks after each vaccine dose. Humoral immunity (antibody titers and neutralizing capacity,VNT%) is analyzed by ELISA at baseline, 2 weeks after each dose, and 6 and 12 months after vaccine. We present the early results of the first 19 subjects. The study is approved by the IRB. Results: 19 subjects (18 in biologics and 1 in IMM) who received 2 doses of the Pfizer-BioNTech vaccine are included. Total IgG antibodies increased 21.13 times after the first dose and 90 times after the second dose. VTN% increased 11.92 times after the first dose and 53.79 times after the second dose. When compared with a healthy control cohort, total IgG antibodies and VTN% were lower in the subjects after the first dose. After the second dose, IgG antibodies increased but remained lower than controls, but VTN% were similar to controls. CD4 and CD8 mean levels had an upward trend after vaccination. Conclusions: Neutralizing capacity response to the vaccine in subjects was similar to a healthy cohort in spite of lower increases in total IgG antibodies. The CD4 and CD8 results observed may support the capacity to mount an effective cellular response in patients on biologics. Larger studies are needed to determine vaccine efficacy in these patients.

Author(s):  
F. P. Tillmann ◽  
H. Still ◽  
Philipp von Landenberg

Abstract Purpose The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown. Methods SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann–Whitney-U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization. Results IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8–4.6) and 4.9 (95% CI 1.0–23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively. Conclusion Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1952
Author(s):  
Andrzej Tretyn ◽  
Joanna Szczepanek ◽  
Monika Skorupa ◽  
Joanna Jarkiewicz-Tretyn ◽  
Dorota Sandomierz ◽  
...  

At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus’s spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1–5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2–3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.


2021 ◽  
Author(s):  
Andrzej Tretyn ◽  
Joanna Szczepanek ◽  
Monika Skorupa ◽  
Joanna Jarkiewicz-Tretyn ◽  
Dorota Sandomierz ◽  
...  

Abstract At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus’s spike protein as a marker of the humoral response in 477 patients and the concentration of gamma interferon as an indicator of a cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1–5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2–3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1383.2-1383
Author(s):  
S. G. Werner ◽  
H. E. Langer ◽  
P. Höhenrieder ◽  
R. Chatelain

Background:PCR (Polymerase Chain Reaction) is generally considered the gold standard for confirming the diagnosis in the early stages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. However, in our rheumatology outpatient clinic we observed a significant discrepancy between clinical evidence of COVID-19 and PCR results.Objectives:Aim of this retrospective study was to analyze the significance of PCR and serologic tests in the diagnosis of COVID-19 (Corona Virus Disease 2019) in a cohort of patients with rheumatic diseases.Methods:Between March 2020 and January 2021, 35 patients with a history of established COVID-19 or typical signs and symptoms were identified on the occasion of a routine rheumatology follow-up examination in our institution. Previous diagnostic work-up in external facilities (results of PCR or antibody testing, imaging) was documented. Antibody ELISA-tests (IgG, IgA, IgM, Euroimmun) were performed in patients reporting typical signs and symptoms of COVID-19 in the past.Results:PCR diagnostics had been performed in 15/35 patients (43%), in 13/35 (39%) at the onset of the first symptoms, in 2 subjects only 2 months later. PCR was positive in 7/13 (54%) of those tested early, but negative in the two patients tested later. In 29/35 patients (83%) SARS-CoV-2-ELISA tests were performed on the occasion of the routine rheumatologic examination (interval between first symptoms and testing on average 98 days, median86, range 4-283 days). In two of the initially negative individuals the second PCR was positive. ELISA tests were positive in all patients. SARS-CoV-2 IgM antibodies were positive in only two patients (however 55 and 71 days after disease onset), n=8/29 (28%) IgG only, n=9/29 (31%) IgG and IgA, n=12/29 (41%) IgA only. In these subjects, IgG antibodies did not develop even in the further course. Antibody titers were in part very high, but in part also very low (only just above the normal value), so even low titers were diagnostic obviously. In all patients with negative PCR, ELISA was positive and retrospectively led to confirmation of the diagnosis. Only in 13/35 patients (37%) diagnosis had been made with the onset of the first symptoms or in the course of clinically manifest disease and had led to appropriate quarantine measures and contact tracing by the health authorities. In contrast, in the majority of patients (63%), the diagnosis of COVID-19 infection was only made retrospectively on the occasion of a routine rheumatologic follow-up. However, 5 of these 22 patients (23%) had quarantined themselves during the symptomatic phase. Titer histories were available from 12 patients. The titer became negative in 7 patients, after a mean of 188 days (median 202, min 51, max 296 days), and remained positive in 5 individuals (mean 190 days, median 191, min 122, max 260 days). The change of the titer was independent of disease severity or antirheumatic therapy.Conclusion:The results suggest that the importance of PCR in the diagnosis of COVID-19 may be overestimated. Therefore, antibody testing for SARS-CoV-2 should be performed in cases of clinical suspicion and negative PCR. In antibody diagnostics, special features were observed compared to other viruses, in particular, in some patients only low antibody titers or the absence of seroconversion with lack of development of IgG antibodies. Normalization of antibody titers in some patients supports the recommendation to vaccinate even after expired COVID-19 disease.Disclosure of Interests:None declared


Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 316
Author(s):  
Ki-Hye Kim ◽  
Noopur Bhatnagar ◽  
Subbiah Jeeva ◽  
Judy Oh ◽  
Bo Ryoung Park ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global vaccination program. The efficacy of many different versions of vaccine candidates and adjuvant effects remain unknown, particularly in the elderly. In this study, we compared the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain in young adult and aged mice, S1 with receptor binding domain, and S2 with fusion domain. Full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Old-aged mice induced SARS-CoV-2 spike-specific IgG antibodies with neutralizing activity after high dose S vaccination. With an increased vaccine dose, S1 was highly effective in inducing neutralizing and receptor-binding inhibiting antibodies, although both S1 and S2 subunit domain vaccines were similarly immunogenic. Adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses. Results of this study provide information in designing SARS-CoV-2 spike vaccine antigens and effective vaccination in the elderly.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shiho Chiba ◽  
Steven J. Frey ◽  
Peter J. Halfmann ◽  
Makoto Kuroda ◽  
Tadashi Maemura ◽  
...  

AbstractThe COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.


2016 ◽  
Vol 43 (2) ◽  
pp. 267-272 ◽  
Author(s):  
Adi Broyde ◽  
Uri Arad ◽  
Noa Madar-Balakirski ◽  
Daphna Paran ◽  
Ilana Kaufman ◽  
...  

Objective.To estimate the longterm humoral response of an antipneumococcal polysaccharide vaccine (PPSV23) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or inflammatory bowel disease (IBD)-associated spondyloarthropathy (SpA), and the effect of demographic and clinical factors and treatment on the longterm efficacy of the vaccine.Methods.A total of 145 consecutive patients treated with biologics [tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) receptor inhibitors] or methotrexate (MTX) participated in this study. Fifteen were excluded because of absent information regarding their vaccination status (n = 9) or because of technical problems in obtaining their serum sample (n = 6). They were diagnosed with RA (n = 63, 48.5%), PsA (n = 29, 22.3%), AS (n = 28, 21.5%), or IBD-associated SpA (n = 3, 2.3%). Their mean age was 54.6 years, and 61.5% were women. Data were collected on the timing of vaccination, demographic and clinical characteristics, and treatment, and patients’ serum antipneumococcal antibody levels were tested.Results.Two-thirds of the patients (67.7%) had received PPSV23 45 months (mean) earlier. Treatment included TNF-α inhibitors (73.9%), IL-6 receptor inhibitors (13.1%), or MTX without a biological treatment (13%). The uptake of vaccination was significantly higher in the older population (> 65 yrs). Vaccinated patients had significantly higher antibody levels compared with vaccine-naive patients. The antibody levels had been preserved after 10 years. MTX use, but not biologics, was associated with significantly lower antibody levels.Conclusion.The longterm efficacy of the PPSV23 vaccination seems to be preserved among patients with RA, PsA, AS, and IBD-associated SpA for at least 10 years. Efficacy is slightly impaired by MTX, but it is not affected by biologics. These findings suggest that revaccination after 5 years might not be needed for all, and testing the antibody titers should be considered to identify those who may benefit from revaccination.


PEDIATRICS ◽  
1981 ◽  
Vol 67 (2) ◽  
pp. 222-229 ◽  
Author(s):  
A. van der Does-van den Berg ◽  
J. Hermans ◽  
J. Nagel ◽  
G. van Steenis

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N= 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.


Sign in / Sign up

Export Citation Format

Share Document