Higher Antibody Concentrations Research Articles

Determination of threshold value of protective level of class G antibodies to SARS-COV‑2 in late phase of immune response in COVID‑19 convalescents

Determining the effectiveness and duration of humoral immunity to SARS-CoV‑2 is of great importance for the management tactics and forecasting of the COVID‑19 pandemic. However, it is important to understand that the high concentration of antibodies, which is characteristic of an acute immune response (including after vaccination), will not persist in its late stage of “memory”. The level of antibodies at the end of the acute phase of the immune response inevitably decreases, and then, having reached a certain limit, it stabilizes in most people.The purpose of this study is to substantiate the threshold value of the “protective” level of antibodies to SARS-CoV‑2 when using the SARS-CoV‑2- IgG-ELISA-BEST reagent system of Vector-Best JSC, Novosibirsk, Russia.The results of our study confirmed that 6–10 and even 18 months after the COVID‑19 disease and 6 months after vaccination, the antibody level positivity index (IP) remained relatively constant and comparable. Taking into account the risks of adverse reactions and complications caused by excessive immunization with repeated administration of the vaccine against a background of high antibody levels, it is advisable to focus on the average value of the level of antibodies of the late phase of the immune response, taking this level as the threshold value of “protective” immunity. The data obtained by us together with the results of foreign authors suggest that both infection with SARS-CoV‑2 and vaccination, in most cases, lead to the formation of long-term humoral immunity, which corresponds to the range of concentration of SARS-CoV‑2-IgG equal to IP=7,77 ± 1,64 or 102,63 ± 29,31 BAU / ml.

Higher Antibody Concentrations in U.S. Health Care Workers Associated with Greater Reactogenicity Post-Vaccination.

Multiple factors may be associated with immune responses to SARS-CoV-2 vaccines. Factors potentially related to magnitude and durability of response include age, time, and vaccine reactogenicity. This study analyzed SARS-CoV-2 IgG spike antibody responses following the second dose of vaccine in healthcare workers (HCWs). Data were collected from participants enrolled in a longitudinal SARS-CoV-2 serology study over a 12-month period. Participants completed a survey documenting symptoms post-vaccination. Serum specimens were tested for SARS-CoV-2 IgG antibodies using the Abbott Architect AdvisdeDx SARS-CoV-2 IgGII assay. Antibody levels were compared against time from second vaccine dose, and symptoms following vaccination. Altogether, 335 women (86.6%) and 52 men (13.4%) participated. Median age was 37 years (IQR 30-43). Overall median antibody level was 2150.80 [1246.12, 3556.98] AU/mL (IQR). Age was not associated with antibody concentration (p-value = 0.10). Higher antibody responses (2253 AU/mL vs. 1506 AU/mL; p = 0.008) were found in HCWs with one or more symptoms after the second dose of the vaccine (n = 311). Antibody responses persisted throughout the study period post-vaccination; statistically significant decreases in antibody responses were observed over time (p < 0.001). Higher antibody response was associated with reactogenicity post-vaccine. Age and sex were not associated with higher antibody responses.

New Onset Generalized Myasthenia Gravis Evolving Following SARS-CoV-2 Infection

During the SARS-CoV-2 (COVID-19) pandemic, the immunogenicity of the virus for various autoimmune complications has been observed. To date, a few reports have been published that raise the possibility of new onset myasthenia gravis (MG) associated with COVID-19 infection. We report a case of a 65-year-old male who developed his initial myasthenic presentation with mild dysarthria 14 days after COVID-19 infection symptomatic onset. His bulbar symptoms, diplopia, and ptosis progressed considerably over the next 1.5 months before he was diagnosed with non-thymomatous MG. Serological tests showed a high concentration of anti-acetylcholine receptor and anti-titin antibodies. He responded well to treatment with pyridostigmine and intravenous immunoglobulin. Reasonable latency from COVID-19 infection and gradual evolvement of myasthenic symptoms makes the causative association probable in this case. To our knowledge, this is the first report of anti-titin antibodies in new-onset MG associated with COVID-19 infection. In the article, we analyze the previously reported cases and summarize the information published to date. We discuss the possible immunological mechanisms behind new onset autoimmune disease following a viral infection and the associated features that raise the suspicion for such a possibility. We also hint at structural homologies between SARS-CoV-2 spike glycoprotein and titin epitopes.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Neutralizing antibodies to SARS-CoV-2 Omicron variant after third mRNA vaccination in health care workers and elderly subjects.

The emergence of SARS‐CoV‐2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS‐CoV‐2‐infected subjects. We measured cross‐protective antibodies against variants in health care workers (HCW, n = 20) and nursing home residents (n = 9) from samples collected at 1–2 months, following the booster (3rd) dose. We also assessed the antibody responses in subjects infected before the Omicron era (n = 38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination, HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta, and Omicron compared to WT virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross‐reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1 month postinfection. High IgG concentrations with cross‐protective neutralizing activity were detected after three Coronavirus Disease 2019 (COVID‐19) vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID‐19 is expected.

COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study

BackgroundThe effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs.MethodsIn this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford–AstraZeneca], BNT162b2 [Pfizer–BioNTech], or mRNA1273 [Moderna]) 6–12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53–92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing.FindingsBetween May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08–0·17; p<0·0001) and tofacitinib (0·43, 0·23–0·81; p=0·0095), but not with ustekinumab (0·69, 0·41–1·19; p=0·18), thiopurines (0·89, 0·64–1·24; p=0·50), or vedolizumab (1·16, 0·74–1·83; p=0·51). mRNA vaccines (3·68, 2·80–4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72–0·87; p<0·0001) with lower antibody concentrations.InterpretationFor patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised.FundingPfizer.

Single-molecule interaction microscopy revealed pH dependent behavior of monoclonal HA antibody

Characterizing on-target specificity is essential for the successful employment of antibodies in research, diagnostics, and therapeutics. In standard assays, antibody specificity is typically evaluated at concentrations much higher than the affinity constant, whereas higher antibody concentrations may lead to non-specific binding. Single-molecule fluorescence imaging can examine the binding behaviors of single antibodies, but the irreversible damage of fluorophores due to photobleaching limits its applicability to high-affinity interactions.

Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina.Seroconversion rates in unexposed subjects after the first and second doses were 40 % and 100 %, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p < 0.0001).The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p = 0.005).A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p = 0.008).Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p < 0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p < 0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects.Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels.Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

Immunogenicity of SARS-CoV-2 vaccines in patients with breast cancer.

Purpose:To explore the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with breast cancer based on type of anticancer treatment.Methods:Patients with breast cancer had anti-spike antibody concentrations measured ⩾14 days after receiving a full SARS-CoV-2 vaccination series. The primary endpoint was IgA/G/M anti-spike antibody concentration. Multiple regression analysis was used to analyze log10-transformed antibody titer concentrations.Results:Between 29 April and 20 July 2021, 233 patients with breast cancer were enrolled, of whom 212 were eligible for the current analysis. Patients who received mRNA-1273 (Moderna) had the highest antibody concentrations [geometric mean concentration (GMC) in log10: 3.0 U/mL], compared to patients who received BNT162b2 (Pfizer) (GMC: 2.6 U/mL) (multiple regression adjusted p = 0.013) and Ad26.COV2.S (Johnson & Johnson/Janssen) (GMC: 2.6 U/mL) (p = 0.071). Patients receiving cytotoxic therapy had a significantly lower antibody titer GMC (2.5 U/mL) compared to patients on no therapy or endocrine therapy alone (3.0 U/mL) (p = 0.005). Patients on targeted therapies (GMC: 2.7 U/mL) also had a numerically lower GMC compared to patients not receiving therapy/on endocrine therapy alone, although this result was not significant (p = 0.364). Among patients who received an additional dose of vaccine (n = 31), 28 demonstrated an increased antibody response that ranged from 0.2 to >4.4 U/ mL.Conclusion:Most patients with breast cancer generate detectable anti-spike antibodies following SARS-CoV-2 vaccination, though systemic treatments and vaccine type impact level of response. Further studies are needed to better understand the clinical implications of different antibody levels, the effectiveness of additional SARS-CoV-2 vaccine doses, and the risk of breakthrough infections among patients with breast cancer.

Immunogenicity of a recombinant hemagglutinin neuraminidase-Porcine rubulavirus produced by Escherichia coli of Porcine rubulavirus gives protective immunity of litter after challenge.

Porcine rubulavirus (PRV) is a contagious virus that affects the Mexican swine industry. This work aimed to evaluate the immunogenicity of an recombinant hemagglutinin neuraminidase-Porcine rubulavirus (rHN-PorPV) candidate vaccine on pregnant sows, and the protective efficacy afforded to their 7-day-old suckling piglets against PRV lethal challenge. Three sows were immunized with rHN-PorPV formulated with immune-stimulating complex (ISCOMs) and two sows with rHN-PorPV protein alone as well as a mock-immunized pregnant sow (negative control). Quantitative ELISA detected a high concentration of anti-rHN-PorPV Immunoglobulin G (IgG) antibodies in sow sera after the second dose of vaccine administered on day 14 until farrowing, showing viral-neutralizing and cross-neutralization activity against different variants of PRV. Sera samples from piglets of immunized sows (with or without adjuvant), showed high concentrations of IgG antibodies. As expected, piglets from the negative control sow (n=5), exhibited severe signs of disease and 100% of mortality after PRV challenge study. Conversely, 75% and 87.5% of the piglets born from the rHN-PorPV and the rHN-PorPV-ISCOMs-immunized sows (n=8), survived, respectively, showing milder PRV clinical signs. Our data indicate that rHN-PorPV candidate vaccine produced in Escherichia coli induces efficient humoral response in pregnant sows and that the maternally derived immunity provides high protection to suckling piglets against PRV lethal challenge.

A Novel Approach to Single Cell Identification, Isolation and Characterisation

The establishment of cell lines capable of producing high-quality monoclonal antibodies is imperative for the development of therapeutic agents and the advancement of biomedical research. Prof Leon WMM Terstappen and his team from the University of Twente in the Netherlands have developed a highly efficient method of identifying and isolating cells that produce high concentrations of specific antibodies. With his team, Prof Terstappen has further honed this method to aid in the refinement of molecular cloning techniques to increase the yield of superior quality monoclonal cell lines.

Comparative Immunogenicity and Effectiveness of mRNA-1273, BNT162b2, and Ad26.COV2.S COVID-19 Vaccines.

BackgroundUnderstanding immunogenicity and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is critical to guide rational use.MethodsWe compared the immunogenicity of mRNA-1273, BNT-162b2, and Ad26.COV2.S in healthy ambulatory adults. We performed an inverse-variance meta-analysis of population-level effectiveness from public health reports in > 40 million individuals.ResultsA single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently undetectable neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Regardless of vaccine, <50% of vaccinees demonstrated CD8+ T-cell responses. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of Beta, Gamma, and Delta strains were poorer regardless of vaccine. In meta-analysis, relative to mRNA1273 the effectiveness of BNT162b2 was lower against infection and hospitalization, and Ad26COV2.S was lower against infection, hospitalization, and death.ConclusionsVariation in the immunogenicity correlates with variable effectiveness of the 3 vaccines deployed in the United States.

Measurement of High Protein Concentrations by Optical Rotation: A Case Study for Monitoring of Monoclonal Antibody Drug Downstream Processes.

Recent advancements in cell engineering and bioreactor engineering have enabled high monoclonal antibody (mAb) concentrations in harvested solutions for the downstream process (DSP). <P>Methods: As many unit operations such as capture chromatography, polish chromatography, membrane filtration, virus inactivation, virus filtration, and concentration by ultrafiltration are involved in DSP, it is crucial to monitor the process carefully in order to perform reliable and stable DSP operations. One of the most important signals (process parameter) to be monitored is the protein concentration CP. Although various methods are available, most of them are not suited for measuring high CP. In this paper, we have developed a method for measuring very high CP by optical rotation (OR). <P>Result: Linear correlations were confirmed between OR and Cp in the range CP = 0 to 80 g/L for mAbs with high repeatability and small variation coefficients. This method was applied to the monitoring of CP in the opaque (colored) solution during the cell culture. The CP by OR was in good agreement with those by the standard Protein A HPLC method. <P> Conclusion: Monitoring of high CP by OR is expected to be an efficient process analytical tool (PAT) for DSP.

Biomarkers of inflammation and cytokine storm: a relationship with the production levels of virus-specific IgG isotype antibodies to SARS-CoV-2 N-protein in COVID-19 present and vaccinated persons

COVID-19 has become a planetary emergency which is seriously threatening human health. Comparative studies can shed light on the molecular mechanisms of the formation of humoral antiviral immunity in persons who have undergone the disease and have been vaccinated against the SARS-CoV-2 virus. Serum levels of biomarkers of inflammation and cytokine storm (procalcitonin, sCD14, sLBP, sTREM1, IL-6, IL-8, IL-10, sWnt5a, TNFα and TNFβ) were determined by enzyme immunoassay. We studied the relationship between the content of biomarkers in blood serum with low and high concentrations of antiviral antibodies, indirect indicators of which are the values of the positivity coefficient (CP). A significant increase in the serum levels of sTREM1, IL-6, and procalcitonin was found in persons with a high CP level after infection. A significant increase in IL-6 and PCT was revealed in persons vaccinated with the Sputnik V vaccine, both with a low level of CP and with a high one. In vaccinated individuals with a low CP level, a significant increase in the sTREM1 content was also observed. It has been shown that the content of sCD14 (presepsin) is significantly lower in vaccinated individuals, both with low and high CP, compared with donors. When studying the correlations between CP and serum biomarkers in vaccinated individuals, a weak inverse correlation was found for sLBP (r = –0.465) and IL-6 (r = –0.437), as well as an average inverse correlation for sTREM1 (r = –0.508).

Immunogenicity of Conjugated and Polysaccharide Pneumococcal Vaccines Administered During Pregnancy or Postpartum to Women With HIV.

Pneumococcal vaccination is recommended in people with HIV, prioritizing PCV. We compared the immunogenicity of PCV-10 and PPV-23 administered antepartum or postpartum. This double-blind study randomized 346 pregnant women with HIV on antiretrovirals to PCV-10, PPV-23, or placebo at 14-34 weeks gestational age. Women who received placebo antepartum were randomized at 24 weeks postpartum to PCV-10 or PPV-23. Antibodies against 7 serotypes common to both vaccines and 1 serotype only in PPV-23 were measured by ELISA/chemiluminescence; B- and T-cell responses to serotype 1 by FLUOROSPOT; and plasma cytokines/chemokines by chemiluminescence. Antibody responses were higher after postpartum versus antepartum vaccination. PCV-10 generated lower antibody levels than PPV-23 against 4 and higher against 1 of 7 common serotypes. Additional factors associated with high postvaccination antibody concentrations were high prevaccination antibody concentrations and CD4+ cells; low CD8+ cells and plasma HIV RNA; and several plasma cytokines/chemokines. Serotype 1 B- and T-cell memory did not increase after vaccination. Antepartum immunization generated suboptimal antibody responses, suggesting that postpartum booster doses may be beneficial and warrant further studies. Considering that PCV-10 and PPV-23 had similar immunogenicity, but PPV-23 covered more serotypes, use of PPV-23 may be prioritized in women with HIV on antiretroviral therapy. NCT02717494.

Humoral response to SARS-CoV-2 vaccines in people living with HIV

PurposeTo describe the humoral immune response to COVID-19 vaccines in people living with HIV and identify factors associated with the magnitude of anti-SARS-CoV-2 antibody concentrations.MethodsRetrospective analysis of electronic patient files in a big single HIV center in Munich, Germany. Non-parametric methods were used for descriptive and comparative statistics. Generalized linear models were used to analyze associations of general and HIV-specific variables with anti-SARS-CoV-2 antibody concentrations after standard vaccination.ResultOverall, 665 people living with HIV were included into the analysis (median age: 53 [IQR: 43; 59]), 560 [84.2%] males). Median concentration of anti-SARS-CoV-2-antibodies was 1400 (IQR 664; 2130) BAU/mL. In 18 (2.7%) subjects, antibody concentrations below the threshold of 34 BAU/mL were found. Among PLWH with CD4 cell count < 200 cells/µL, median anti-SARS-CoV-2-Abs were 197 (IQR 44.6; 537.2) as compared to 1420 (IQR 687; 2216) for the group ≥ 200 cells/µL (p < 0.001). In a cumulative logit model, a vaccination scheme including an mRNA vaccine [OR: 4.64 (3.58; 6.02)], being female [OR: 2.14 (1.76; 2.61)], and having higher CD4 cells [OR per 100 cells/µL: 1.06 (1.04; 1.08)] were significantly associated with anti-SARS-CoV-2 antibody concentrations in higher quartiles, when adjusted for the time after vaccination.ConclusionWe found a robust antibody response in people living with HIV undergoing standard vaccination against SARS-CoV-2. mRNA-containing vaccination schemes, being female, and having a higher CD4 cell count was associated with a higher concentration of antibodies in people living with HIV in our study sample. Particularly in the subgroup with CD4 cell counts < 200 cells/µL, antibody response was poor.

Маркери імунного запалення у хворих на неалкогольну жирову хворобу печінки коморбідну із хронічним обструктивним захворюванням легень

The purpose of the study was to determine markers of immune inflammation in patients with nonalcoholic fatty liver disease combined with chronic obstructive pulmonary disease. Materials and methods. The observation revealed 82 patients who were treated in the pulmonology and gastroenterology department of the Andriy Novak Transcarpathian Regional Clinical Hospital during 2018-2020 with a diagnosis of nonalcoholic fatty liver disease and chronic obstructive pulmonary disease II group B and C. Among the examined there were 61.0% (50) men and 40.0% (32) women. The average age was 57.8±1.5 years old. Results and discussion. As a result of the conducted research it is established that increased levels of chronic immune inflammation markers were observed in all examined with significant increase in patients with a comorbid condition. The highest concentrations of C-reactive protein were found in patients with nonalcoholic fatty liver disease combined with chronic obstructive pulmonary disease with frequent exacerbations and hospitalization, and exceeded the normal values by 8.3 times. The levels of tumor necrosis factor-α and neopterin in patients with frequent exacerbations of chronic obstructive pulmonary disease and hospitalization were by 2.7 times and 1.9 times higher than in patients with a small number of exacerbations and by 3.2 and 3.9 times higher than in patients with nonalcoholic fatty liver disease without chronic obstructive pulmonary disease. The indexes of interleukin-6, transforming growth factor-β, the number of IgG antibodies to neutrophil elastase and the level of tissue inhibitor of matrix proteinases-1 remain consistently high in all patients with combined pathology of nonalcoholic fatty liver disease and chronic obstructive pulmonary disease regardless of the frequency of exacerbations, thus supporting inflammation even in remission. Elastase antibody levels correlate directly with the levels of the tissue metalloproteinase-1 inhibitor and increase with the degree of severety of fibrosis, which may indicate a high level of serum neutrophil elastase activity in patients with nonalcoholic fatty liver disease in combination with chronic obstructive pulmonary disease and its participation in fibrosis. Conclusion. Patients with nonalcoholic fatty liver disease in combination with chronic obstructive pulmonary disease showed an increased level of chronic systemic inflammation of low intensity based on the analysis of C-reactive protein, tumor necrosis factor-α, neopterin and interleukin-6 compared with nonalcoholic fatty liver disease without chronic obstructive pulmonary disease even in remission, which indicates an aggravating course of the disease in combination of two pathologies. Stably high concentration of IgG antibodies to neutrophil elastase may indirectly indicate the maintenance of the activity of this enzyme in the serum of patients with nonalcoholic fatty liver disease in chronic obstructive pulmonary disease and confirms its participation in liver fibrogenesis

Sequential Profiling of Anti-SARS CoV-2 IgG Antibody in Post COVID-19 Patients.

Upon SARS CoV-2 infection, humoral immune system triggers production of anti-SARS CoV-2 IgM and IgG antibodies. Currently, antibodies against SARS CoV-2 spike protein receptor binding domain play a central role in disease protection, making them potential target for in vitro diagnostics applications. This study determines the expression level and sustainability of anti-receptor binding domain (RBD) SARS CoV-2 IgG in post COVID-19 patients. Anti-RBD SARS CoV-2 IgG antibodies in patient serum were analysed by standardised indirect ELISA using SARS CoV-2 spike receptor binding domain protein and HRP conjugated anti-human IgG antibody (anti-h IgG). The study was conducted using 35 adult patient samples with confirmed SARS CoV-2 infection. Additionally, correlation between antibody response after each stage and disease symptoms in post COVID-19 patients were studied. Maximum antibody titre was seen at Day 40 and decreased relatively to Day 180 in antibody positive samples when compared with controls. Overall, more IgG antibody expression is observed in patients who suffered from loss of smell and taste at Day 40. 71% of the positive subjects in this study showed high SARS CoV-2 IgG antibody concentration of above 10 ng/mL and 37% showed strong antibody concentration above 20 ng/mL at the peak of seroconversion.

Inhalation monoclonal antibody therapy: a new way to treat and manage respiratory infections.

The route of administration of a therapeutic agent has a substantial impact on its success. Therapeutic antibodies are usually administered systemically, either directly by intravenous route, or indirectly by intramuscular or subcutaneous injection. However, treatment of diseases contained within a specific tissue necessitates a better alternate route of administration for targeting localised infections. Inhalation is a promising non-invasive strategy for antibody delivery to treat respiratory maladies because it provides higher concentrations of antibody in the respiratory airways overcoming the constraints of entry through systemic circulation and uncertainity in the amount reaching the target tissue. The nasal drug delivery route is one of the extensively researched modes of administration, and nasal sprays for molecular drugs are deemed successful and are presently commercially marketed. This review highlights the current state and future prospects of inhaled therapies, with an emphasis on the use of monoclonal antibodies for the treatment of respiratory infections, as well as an overview of their importance, practical challenges, and clinical trial outcomes. Key points • Immunologic strategies for preventing mucosal transmission of respiratory pathogens.• Mucosal-mediated immunoprophylaxis could play a major role in COVID-19 prevention.• Applications of monoclonal antibodies in passive immunisation.

B and T cell response to SARS-CoV-2 vaccination in health care professionals with and without previous COVID-19.

SummaryBackgroundIn recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies.MethodsIn a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon-γ release assays and intracellular flow cytometry. Vaccine-related side effects were captured.FindingsPrior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein.InterpretationHerein, we corroborate recent findings suggesting that in convalescents a single vaccine dose is sufficient to boost adequate in vitro neutralisation of SARS-CoV-2 and therefore may be sufficient to induce adequate protection against severe COVID-19. New spike mutated virus variants render the highly conserved nucleocapsid protein – eliciting strong SARS-CoV-2 specific T cell immunity – an interesting additional vaccine target.FundingChristian Doppler Research Association, Johannes Kepler University Linz