Changes In Titers Research Articles

Therapeutics and prophylactic efficacy of novel lytic Escherichia phage vB_EcoS_PJ16 against multidrug-resistant avian pathogenic E. coli using in vivo study.

Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis, which causes significant economic losses to the poultry industry. The growing resistance of bacteria to antibiotics is a major global public health concern. However, there is limited data on the efficacy of phage therapy in effectively controlling and treating APEC infections. In this study, a novel lytic Escherichia phage, vB_EcoS_PJ16, was isolated from poultry farm wastewater and characterized in both in vitro and in vivo conditions. Transmission electron microscopy analysis revealed the presence of an icosahedral head and a long non-contractile tail, classifying the phage under the Caudoviricetes class. Host range determination showed that Escherichia phage vB_EcoS_PJ16 exhibited lytic activity against multiple strains of pathogenic E. coli, while no significant signs of lysis for Klebsiella pneumoniae, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus. Biophysical characterization revealed that the isolated phage was sturdy, as it remained viable for up to 300days at temperatures of 30°C, 37°C, and 42°C and for up to 24h at pH 5 to 11, with only minor changes in titer. Kinetic analysis at multiplicity of infection (MOI) 0.1 showed a latency period of about 20min and a burst size of 26.5 phage particles per infected cell for phage vB_EcoS_PJ16. Whole genome sequencing unveiled that the phage vB_EcoS_PJ16 genome consists of a double-stranded linear DNA molecule with 57,756bp and a GC content of 43.58%. The Escherichia phage vB_EcoS_PJ16 genome consisted of 98 predicted putative ORFs, with no transfer RNA identified in the genome. Among these 98 genes, 34 genes were predicted to have known functions. A significant reduction in APEC viability was observed at MOI 100 during in vitro bacterial challenge tests conducted at different MOIs (0.01, 1, and 100). In vivo oral evaluation of the isolated phage to limit E. coli infections in day-old chicks indicated a decrease in mortality within both the therapeutic (20%) and prophylactic (30%) groups, when compared to the control group. The findings of this study contribute to our current knowledge of Escherichia phages and suggest a potentially effective role of phages in the therapeutic and prophylactic control of antibiotic-resistant APEC strains.

Synthesis and pharmacodynamic evaluation of naphthalene derivatives against influenza A virus in vitro and in vivo

Influenza A virus is a highly mutable pathogenic pathogen that could cause a global pandemic. It is necessary to find new anti-influenza drugs to resist influenza epidemics due to the seasonal popularity of a certain area every year. Naphthalene derivatives had potential antiviral activity. A series of naphthalene derivatives were synthesized via the metal-free intramolecular hydroarylation reactions of alkynes. Evaluation of their biological efficacy showed that compound 2-aminonaphthalene 4d had better antiviral activity in vitro than ribavirin. By studying the mechanism of action of 2-aminonaphthalene 4din vivo and in vitro, we found that 4d had antiviral activity to three different subtype influenza viruses of A/Weiss/43 (H1N1), A/Virginia/ATCC2/2009 (H1N1) and A/California/2/2014 (H3N2). Compound 4d had the best effect after viral adsorption, and mainly played in the early stage of virus replication. 2-Aminonaphthalene 4d could reduce the replication of virus by inhibiting the NP and M proteins of virus. Compound 4d cut down ROS accumulation, autophagy and apoptosis induced by influenza virus. Inflammatory response mediated by RIG-1 pathway were suppressed in the cell and mice. In addition, the pathological changes of lung tissue and virus titer in mice were reduced by the administration of 4d. Therefore, naphthalene derivative 4d is a potential drug for the treatment of influenza A virus infection.

The relationship of maternal hepatitis B e antigen and response to vaccination of infants born to women with chronic infection

BackgroundThe relationship of maternal HBeAg and infants’ response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection.Methods3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups.ResultsThe infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7–12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8–1000.0) vs 719.67(208.1–1000.0) at 7–12 months (Z = -3.049, P = 0.002) and 783.5(227.8–1000.0) vs 891.4(234.0–1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139–1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002–1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants.ConclusionsMaternal HBeAg did affect the infants’ immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.

Development of Hemagglutinin-Neuraminidase Homologous Peptides as Novel Promising Therapeutic Agents Against Peste des Petits Ruminants Virus.

The lack of specific antiviral therapy and complications associated with the existing peste des petits ruminants (PPR) vaccines accentuates the search of novel antiviral blocking agents in order to curtail the PPR infection at initial level. The synthetic hemagglutinin-neuraminidase (HN) homologous peptides may compete with the natural HN protein of PPR virus for binding to signaling lymphocytic activation molecule (SLAM) receptor, consequently, may disrupt peste des petits ruminants virus (PPRV) at entry level. Therefore, insilico analysis, synthesis, purification and subsequent characterization of HN homologous peptides were conducted in this study. The HN homologous peptides were synthesized by means of solid phase chemistry and were purified by reversed-phase-high performance liquid chromatography. The mass as well as sequence of HN homologous peptides were assessed by mass spectroscopy while its secondary structure was elucidated by circular dichroism spectroscopy. The binding (interaction) efficacy of HN homologous peptides with PPRV antibodies was assessed via indirect enzyme linked immunosorbent assay, visual detection test (red wine to purple), bathochromic shift under UV-Vis spectrophotometry and lateral flow immunochromatographic strip test. The antiviral properties and cytotoxicity of these peptides were also assessed in B95a cell line with changes in cytopathic effect and titer of PPRV (Sungri/96). The presence of green fluorescein isothiocyanate over the B95a cell surface pointed towards the binding of HN homologous peptides with surface SLAM receptor. Moreover, the intact beta sheet configuration in water and lower cytotoxicity [cytotoxic concentration 50 (CC50) > 1000µg/ml] of these peptides signifies its in vivo use. Among HN homologous peptides, the binding efficacy and antiviral properties of pep A was relatively high in comparison to pep B and Pep ppr peptides. The prerequisite concentration of HN homologous peptides (pep A = 12.5µg/ml; pep B = 25µg/ml; pep ppr = 25µg/ml) to exemplify its antiviral effect was much lower than its CC50 level. Hence, this study signifies the therapeutic potential of synthetic HN homologous peptides.

Brief report: can COVID-19 infection trigger rheumatoid arthritis-associated autoimmunity in individuals at risk for the disease? A nested cohort study.

To investigate the association between severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) infection and subsequent development of autoimmunity or pre-clinical manifestations associated with rheumatoid arthritis (RA) in at risk population. This is a nested study within a prospective cohort of first-degree relatives of RA patients (RA-FDR). Participants are tested for RA-associated autoantibodies (anti-citrullinated peptide antibodies (ACPA)/rheumatoid factor (RF)) and clinical signs and symptoms suggestive of early disease. SARS-CoV-2 infections were self-reported between March 2020 and January 2023. All individuals with a pre-pandemic (sample 1) and a post-pandemic sample (sample 2) were included in the analysis. The exposure of interest was self-reported SARS-CoV-2 infection. The primary outcome was a clinically significant change in RA-associated autoantibody serum titers. Secondary outcomes included: becoming seropositive, becoming symptomatic, developing classifiable RA. Among 168 RA-FDRs, 109 reported a SARS-CoV-2 infection between sample 1 and sample 2. During this period, 2 RA-FDRs (1.2%) became anti-CCP2 seropositive, none became anti-CCP3 IgG positive, 6 (3.6%) became RF IgM seropositive, 1 became (0.6%) RF IgA seropositive, 19 (11.3%) became symptomatic and none developed classifiable RA. SARS-CoV-2 infection was not significantly associated with increases in RA autoantibody titers or with secondary outcomes. We could not detect an association between SARS-CoV-2 infection and subsequent development of RA-associated autoimmunity, nor signs or symptoms of RA in an at risk population. These findings do not support the hypothesis that SARS-CoV-2 infections triggers the immune onset of RA.

Alterations in Aquaporin-4-IgG Serostatus in 986 Patients: A Laboratory-Based Longitudinal Analysis.

This study was undertaken to investigate factors associated with aquaporin-4 (AQP4)-IgG serostatus change using a large serological database. This retrospective study utilizes Mayo Clinic Neuroimmunology Laboratory data from 2007 to 2021. We included all patients with ≥2 AQP4-IgG tests (by cell-based assay). The frequency and clinical factors associated with serostatus change were evaluated. Multivariable logistic regression analysis examined whether age, sex, or initial titer was associated with serostatus change. There were 933 patients who had ≥2 AQP4-IgG tests with an initial positive result. Of those, 830 (89%) remained seropositive and 103 (11%) seroreverted to negative. Median interval to seroreversion was 1.2 years (interquartile range [IQR] = 0.4-3.5). Of those with sustained seropositivity, titers were stable in 92%. Seroreversion was associated with age ≤ 20 years (odds ratio [OR] = 2.25; 95% confidence interval [CI] = 1.09-4.63; p = 0.028) and low initial titer of ≤1:100 (OR = 11.44, 95% CI = 3.17-41.26, p < 0.001), and 5 had clinical attacks despite seroreversion. Among 62 retested after seroreversion, 50% returned to seropositive (median = 224 days, IQR = 160-371). An initial negative AQP4-IgG test occurred in 9,308 patients. Of those, 99% remained seronegative and 53 (0.3%) seroconverted at a median interval of 0.76 years (IQR = 0.37-1.68). AQP4-IgG seropositivity usually persists over time with little change in titer. Seroreversion to negative is uncommon (11%) and associated with lower titers and younger age. Seroreversion was often transient, and attacks occasionally occurred despite prior seroreversion, suggesting it may not reliably reflect disease activity. Seroconversion to positive is rare (<1%), limiting the utility of repeat testing in seronegative patients unless clinical suspicion is high. ANN NEUROL 2023;94:727-735.

Longitudinal Observation of Immune Response for 23 Months in COVID-19 Convalescent Patients After Infection and Vaccination.

To better understand dynamic changes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune response, a prospective, single-center, cohort study was conducted on longitudinal immune response in 34 COVID-19 convalescent patients over 23 months in Chongqing. Two blood samples from convalescent patients were collected, first sample collected during 10-13 months (M10-13) after infection (pre-SARS-CoV-2 vaccination) and second sample collected during 20-23 months (M20-23) after infection (post-SARS-CoV-2 vaccination). The SARS-CoV-2-specific humoral and cellular immunity were traced by testing total antibody (Ab), anti-nucleocapsid (NP) immunoglobulin M (IgM), anti-NP immunoglobulin G (IgG), and anti-spike (S) IgG Abs, lymphocyte subset count, and Th1 cytokines. Healthy donors (30) were also included in the study as the uninspected healthy controls. Our data showed significant change in mean titer of SARS-CoV-2-specific Ab response from M10-13 to M20-23 included, namely, SARS-CoV-2-specific total Ab as 219 AU/mL increasing to 750.9 AU/mL; anti-NP IgM as 3.5 AU/mL decreasing significantly (p < 0.001) to 0.6 AU/mL; anti-NP IgG as 7.9 AU/mL increasing to 87.1 AU/mL; and anti-S IgG as 499.0 RU/mL increasing to 1,802.3 RU/mL. Our observations suggested that one vaccine dose might have been sufficient for COVID-19 convalescent patients. Larger sample sizes are needed to compare better immune effect of protein subunit vaccine. Besides, compared to healthy donors, patients had decreased CD3+ and CD8+ T lymphocyte counts during two periods. Patients had most cytokines recovered normally within 2 years, but IL-6 level was significantly elevated; however, IL-6 was negatively correlated with IgM and positively correlated with IgG. Changes in cytokines might have been caused by SARS-CoV-2 infection or vaccination. Patients with comorbidities were associated with decreased CD3+ and CD8+ T lymphocytes and lower Ab titers following SARS-CoV-2 vaccination. Vaccination enormously increased humoral immunity beneficial in COVID-19 convalescent patients. Elderly COVID-19 convalescent patients with comorbidities needed more attention.

Immunoglobulin G follow-up and immune response longevity analysis in SARS-CoV-2 convalescent patients and vaccinated individuals: A longitudinal analysis.

Although the detection of immunoglobulin G (IgG) molecules has long been considered to be crucial for successful humoral immune defence against infections and harmful metabolites, it has become increasingly important in relation to SARS-CoV-2 research. To compare longitudinal changes in IgG titres in post-infection and post-vaccination Iraqi participants, and to estimate the protective benefits of the two principal vaccines used in Iraq. This quantitative study used samples from SARS-CoV-2 recovered patients (n= 75), those vaccinated with two doses of Pfizer or Sinopharm vaccine (n= 75), and healthy unvaccinated individuals (n= 50) who formed a control group. Participant ages (range 20-80 years) and sex (52.7% men, 47.3% females). An enzyme-linked immunosorbent assay was used to measure IgG. IgG antibody levels peaked in the first month and tapered off in the following three months in both convalescent and vaccinated groups. The latter showed a significant decrease in IgG titres than in the convalescent group. Samples from the group given the mRNA vaccination that targeted spike (S) proteins might have a cross-reactivity between nucleocapsid (N) and spike (S) proteins. Participants who had recovered from or who were vaccinated against SARS-CoV-2 exhibited a protective, persistent and durable humoral immune response for at least a month. This was more potent in the SARS-CoV-2 convalescent group compared to the vaccinated cohort. The IgG titres decayed faster after vaccination with Sinopharm than following the Pfizer-BioNTech vaccine.

Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia

BackgroundAn effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited.MethodsWe conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above −10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed.ResultsA total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, −0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group).ConclusionsFor all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident. (Funded by the U.K. Foreign, Commonwealth, and Development Office and others; ClinicalTrials.gov number, NCT03964012.)

Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers

SARS-CoV-2-specific antibody measurement is important for evaluating COVID-19 vaccine efficacy. We quantified and compared anti-spike (S) antibodies using different commercial immunoassays. We tested serum samples from 70 SARS-CoV-2-naive health care workers 2 weeks after vaccination with a single dose of BNT162b2, 2 and 4 weeks, and 3 months after the second dose of BNT162b2. The following quantitative assays were used: Roche Elecsys Anti-SARS-CoV-2 S (Roche-S), Abbott SARS-CoV-2 IgG II Quant [Abbott-IgG(S)], and Abbott SARS-CoV-2 IgM (Abbott-IgM). All samples tested positive for Roche-S and Abbott-IgG antibodies after the second dose, with 83.6% Abbott-IgM positive rate. Roche-S and Abbott-IgG(S) correlated significantly in all samples (r = 0.920, p < 0.0001), and the Roche-S and Abbott-IgG(S) assay showed a strong correlation with each other at each time point after vaccination. Roche-S and Abbott-IgG(S) antibody titers were correlated with age; their rate of decline was age-dependent in males but not in females. Abbott-IgG(S) antibody titers decreased from 2 weeks after the second dose. Roche-S antibody titers peaked 2 weeks after the second dose in 76.2% of the participants; the titers recovered 3 months post-vaccination after declining at week 4 in 40.7% of the participants. The concordance between Roche-S and Abbott-IgG(S) antibody titers over time was 47.5%. Most participants presented significantly high Roche-S and Abbott-IgG(S) antibody titers after immunization. Some measurements were inconsistent with titer changes between these assays, possibly because of differences in the immunoglobulin-specificity of the kits.

Prognostic impact of perioperative change in serum p53 antibody titers in esophageal squamous cell carcinoma.

The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2months vs. 36.7months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.

Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

Clinical usefulness of anti-nuclear antibody in childhood: real-world experience at a tertiary care center : Usefulness of ANA in pediatric autoimmune diseases.

We evaluated the reasons for requesting anti-nuclear antibody (ANA) analysis in clinical practice at a tertiary center and the performance of ANA in pediatric autoimmune diseases. Patients under 18years of age who underwent ANA testing for various symptoms between 2013 and 2017 were included. We retrieved data from medical records, including demographic and clinical characteristics, diagnoses, ANA results, titers, and staining patterns. The performance assessment tools were calculated according to the ANA titer for autoimmune diseases. Risk factors for autoimmune diseases in ANA-positive patients were evaluated using logistic regression analysis. Changes in ANA titer and seroconversion were evaluated using repeated ANA analyses. A total of 3812 patients underwent ANA. Medical records of 3320 patients were obtained. The rate of ANA positivity was 27.4%. ANA was requested most frequently because of musculoskeletal findings in 1355 patients (40.8%). Juvenile idiopathic arthritis (n = 174, 20.2%) was the most common diagnosis in ANA-positive patients, followed by systemic lupus erythematosus (n = 52, 6%). For autoimmune diseases, a titer of ≥ 1:100, a sensitivity of 40.1%, and a specificity of 77.1% were observed. At a titer ≥ 1:1000, the sensitivity and specificity were 24.1% and 89%, respectively. Homogeneous staining was an additional risk factor for autoimmune diseases in ANA-positive patients by multivariate logistic regression analysis (OR [95% CI]: 4.562 [3.076-6.766], p < 0.001). Conclusion: Our results revealed that the performance of the ANA test in diagnosing autoimmune diseases in pediatric clinical practice was poor. Therefore, clinical findings should be carefully evaluated before ANA testing is performed. What is Known: • ANA can be detected in systemic autoimmune rheumatic diseases. • The diagnostic role of ANA is controversial, especially in childhood. What is New: • One in four patients who requested the ANA test had an autoimmune disease. • Less than half of patients with an autoimmune disease had ANA positivity.

Comparison of high-dose IVIG and rituximab versus rituximab as a preemptive therapy for de novo donor-specific antibodies in kidney transplant patients

De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).

Changes in antibody titres and comparative efficacy of some unconventional remedies in mitigating the effects of infectious bursal disease virus infection in pullet chicks

Unconventional remedies are used by farmers against infectious bursal disease (IBD). This study assessed changes in IBD antibody titres and efficacy of some unconventional remedies used by farmers against IBD. Day old ISA brown pullets were assigned into eight groups (A-H) and inoculated with a very virulent IBD virus (vvIBDV) at 21 days of age as follows; group A - administered aqueous leaf extract of Kaya senegalensis (KS); B, C, D, E, and F administered remedies designated as SEV, ENP, ASMS, DLP, and OVX, respectively; G, and H were negative, and positive control, respectively. Changes in IBD antibody (Ab) titres, clinical signs, morbidity and mortality rates, gross lesions, weights and organ ratios of bursal (BF), spleen (S) and thymus (T) were assessed. There were protective levels of Ab in groups of chicks at 2 and 7 days of age. SEV and ASMS potentiated Ab response to vvIBDV; SEV mitigated the severity of clinical signs, morbidity and mortality rates, gross lesions and changes in body and BF weights and SBR; KS clinical signs, morbidity and mortality rates, BF weight and BBR; ENP morbidity rate, spleen and thymus weights and TBR; ASMS thymus weight and TBR; DLP gross lesions, BF weight and BBR; OVX body, spleen weights and SBR. The remedies demonstrated varied actions against VVIBDV infection. SEV and KS leaves could be administered at the onset of IBD outbreak and before IBD vaccination. Processing of KS leaves to reduce concentration of antimetabolites is recommended.

Chronic opioid use is associated with higher flu vaccine induced Ab response in HIV+ and HIV− individuals.

Abstract Opioid dependence is frequent in people with HIV (PWH), but impact of opioids on immune system of PWH is unknown. This study tested the hypothesis that chronic opioid use exacerbates known impairment of flu vaccine responses in PWH. Chronic opioid users were compared to non-opioid users in HIV+ and HIV− groups termed HIV+OP+ (n=28), HIV-OP+ (n=55), HIV+OP− (n=53), HIV-OP− (controls, n=58). HIV+ individuals were on ART with plasma virus load &amp;lt;200 copies/mL. Flu antibody titers were determined at pre- (T0) and 4 weeks post (T2) seasonal quadrivalent influenza vaccinations (2020–2022) by hemagglutination inhibition (HAI) along with a plasma cytokine score at T0. Vaccine response (VR) was defined as a 4-fold change (FC) in titer from T0 to T2. In Kruskal Wallis analysis, all 4 groups had increases in HAI titer from T0 to T2 (p&amp;lt;0.01 to p&amp;lt;0.0001) for antigens (H1N1, H3N2, B Victoria) and whole vaccine. HIV+ status was associated with decreased responses to all antigens but OP+ status in HIV+ and HIV− had higher response than HIV+OP−, both in T2/T0 FC and T2 titer for one or more vaccine antigens (p&amp;lt;0.05 to p&amp;lt;0.001). In regression analysis controlling for demographics, opioid use was associated with increased response to H1N1 and B Yamagata antigens. In a random forest model, predicted probability of VR was lower for HIV+ status and higher for OP+ status. Cytokine score was highest in HIV+OP+. Results of quantitative Ab response to flu vaccine refute our hypothesis that flu vaccine response would be impaired in PWH who chronically use opioids. Qualitative assessments of Ab and mechanism of opioid intersection with B cell function are ongoing to understand if opioid use overcomes humoral immune deficits in PWH.

Association of B cell Subsets and Aquaporin-4 antibody titers with Disease Activity in Participants in the N-MOmentum trial Receiving Inebilizumab Treatment (S5.005)

Association of B cell Subsets and Aquaporin-4 antibody titers with Disease Activity in Participants in the N-MOmentum trial Receiving Inebilizumab Treatment (S5.005)

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

Longitudinal Changes in IgG-Type SARS-CoV-2 Antibody Titers after COVID-19 Vaccination and a Prominent Increase in Antibody Titers When Infected after Vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers level and duration of elevated levels are considered important indicators for confirming the efficacy of coronavirus disease 2019 (COVID-19) vaccines. The objective of this study was to demonstrate the changes in antibody titers after the second and third doses of the COVID-19 vaccine, and to determine the antibody titers in cases of spontaneous infection with SARS-CoV-2 after vaccination. From June 2021 to February 2023, IgG-type SARS-CoV-2 antibody titers were measured in 127 participants, including 74 outpatients and 53 members of staff, at the Osaka Dental University Hospital (64 males and 63 females, mean age 52.3 ± 19.0 years). Consistent with previous reports, the SARS-CoV-2 antibody titer decreased with time, not only after the second dose but also after the third dose of the vaccine if there was no spontaneous COVID-19 infection. We also confirmed that the third booster vaccination was effective in increasing the antibody titer. A total of 21 cases of natural infections were observed after administering two or more doses of the vaccine. Thirteen of these patients had post-infection antibody titers exceeding 40,000 AU/mL, and some cases continued to maintain antibody titers in the tens of thousands of AU/mL even after more than 6 months had passed since infection. The rise in and duration of antibody titers against SARS-CoV-2 are considered important indicators for confirming the efficacy of novel COVID-19 vaccines. A longitudinal follow-up of antibody titers after vaccination in larger studies is warranted.

Aflatoxin B1 can aggravate BALB/c mice allergy to ovalbumin through changing their Th2 cells immune responses

Foods contaminated by Aflatoxin B1 (AFB1) frequently happen in the world and can cause a lot healthy damages to human beings, meanwhile, some of these foods are easily irritate food allergy. To investigate the effect of AFB1 exposure on food allergy, three doses of AFB1 were set, including 0.3 μg/kg · bw (LDAF), 7.5 μg/kg · bw (MDAF), and 100.0 μg/kg · bw (HDAF), respectively; food allergy model was constructed by the BALB/c mice allergy to ovalbumin (OVA). The changes of titer in OVA-specific immunoglobulin E (IgE), IgG, IgG1, IgG2a, as well as level of the mMCP-1 in sera were determined by enzyme linked immunosorbent assay (ELISA), respectively; the levels of interleukin (IL-4, IL-5, IL-13) and interferon (IFN)-γ in spleen were separately assessed using ELISA kits, and their relative genes expression were verified by Real-time fluorescence quantitative PCR (Q-PCR); the population of Th1/Th2/Treg cells were analyzed by flow cytometry. Results showed that when OVA-allergic mice were exposed to AFB1, the production of OVA-specific IgE, IL-4, IL-5 and IL-13, and mMCP-1 were all increased, whereas the level of IFN-γ was decreased; the Th1/Th2 balance was disrupted and the development of Th cells tilted to the Th2 phenotype. The study would contribute to further understand the risk of fungal toxins in food allergy.