Serological Response Research Articles

Elevated IL-10 serum levels are associated with slower serological response following syphilis treatment during pregnancy.

Approximately 50% of pregnant individuals treated for syphilis do not achieve a decline in non-treponemal titers by delivery. The serological response in pregnant persons is significantly slower compared to non-pregnant individuals, with unclear pathogenesis and clinical significance. This study aimed to determine the association between the host immune response and serological outcome in pregnant individuals with syphilis. Twenty-four females with early syphilis, including 14 pregnant individuals, were included. Pro-inflammatory and regulatory cytokines (IFN-γ, TNF-α, IL-4, IL-1β, IL-10, TGF-β) were measured before treatment and 6 months after penicillin injection. The median time to serological cure was 5months for pregnant individuals and 2months for non-pregnant females. Pregnant individuals had significantly higher serum levels of IL-10 and TGF-β at baseline and at 6months post-treatment compared to non-pregnant individuals (p < .05). A robust regulatory immune response to syphilis may be associated with a slower serological response to therapy during pregnancy.

Safety and immunogenicity of the yellow fever vaccine for patients with end-stage renal disease.

In December 2016, an outbreak of sylvatic yellow fever (YF) occurred in the non-endemic areas of the south-eastern region of Brazil. The immune response to the yellow fever vaccine and its safety in individuals with chronic kidney disease (CKD) living in YF-endemic regions are not thoroughly understood. The objective of this study is to assess the incidence of adverse events and the serological response after primary vaccination with the 17DD-YF vaccine in CKD patients undergoing dialysis. This was a multicenter, retrospective cohort study involving 223 individuals with CKD who were on dialysis after primary vaccination against YF. Clinical and epidemiologic characteristics were collected and the vaccine adverse event (VAE) were assessed. Around 35 months after vaccination, the serological response was evaluated in 71 (32%) patients using neutralization tests. No serious VAE occurred in any patient. Local reactions were reported in 13 individuals (5.8%), while 6 (2.7%) reported generalized systemic reactions and 205 (91.9%) did not display any VAE. No clinical or epidemiologic characteristic predicted the occurrence of VAE. Adequate serological response was found in 38% of participants and none of the clinical or epidemiological characteristics were associated with immunogenicity. The outcomes of our study suggest that the yellow YF vaccine is well-tolerated in CKD patients undergoing dialysis, but it does not induce adequate immune response. Future research should focus on evaluating both cellular and humoral immune responses following administration of various doses of the YF vaccine.

Serological response to avian influenza viruses among occupationally exposed population in Taiwan, a longitudinal cohort study, 2021-2023.

The Taiwan Centers for Disease Control (TCDC) initiated longitudinal sero-epidemiological surveillance of avian influenza viruses (AIVs) targeting poultry workers exposed on affected farms since 2021. Convalescent-phase serum samples were collected from these workers 21-28 days post-outbreak identification. TCDC recontacted participants in subsequent years for repeat serological sampling. Hemagglutination inhibition (HI) assays were used to test against representative strains of AIV A/H5 2.3.4.4c and A/H5 2.3.4.4b. By the end of 2023, a 2-year cohort of 59 participants and a 3-year cohort of 61 participants were established. None of them had laboratory-confirmed infection. HI titers against AIV A/H5 2.3.4.4c remained low from 2021 to 2023. For AIV A/H5 2.3.4.4b, HI titer remained low from 2021 to 2022 but increased in more than half of the participants (60%, 72/120) in 2023. This change parallels the increasing AIV A/H5 2.3.4.4b burden indicated by increased outbreaks and warrants continuous monitoring.

Long-term serological response and boostability of intradermal rabies immunization: A retrospective chart review.

Rabies vaccines in Canada are currently labeled for intramuscular use only; however, intradermal vaccine administration may be equally effective. This study aims to assess the immediate and long-term (≥ 2years) serological response and boostability of intradermal administration of rabies vaccine for pre-exposure prophylaxis. This retrospective cohort study was conducted using data from electronic medical records at the Winnipeg Regional Health Authority Travel Health & Tropical Medicine Services Clinic. Individuals ≥ 18years of age at time of vaccination who received at least 3 × 0.1mL doses of intradermal rabies vaccine were included. All charts were reviewed to extract post-primary immunization and post-booster serology results, and t-tests were conducted to evaluate seroprotection (defined as serology ≥ 0.5IU/mL). A total of 324 individuals received an intradermal rabies primary pre-exposure vaccination series with follow-up serology within 90days. Seroprotection was observed in 96% (GMT = 3.36IU/mL, 95% CI 3.07-3.68). Of these, 68 had serology results 1.8-2.5years later, with seroprotection declining to 44% (GMT = 0.52IU/mL, 95%CI 0.41-0.65). However, 100% seroprotection was observed in those who received an intradermal booster dose at ≥ 2years with follow-up serology (n = 20, GMT = 4.7IU/mL, 95%CI 3.7-6.2). Intradermal administration of a primary pre-exposure rabies vaccine series demonstrates a strong serological response. While titers decline over time, the robust serological response demonstrated after a single intradermal booster vaccine dose suggests that a strong anamnestic immune response was maintained. This finding supports existing evidence that intradermal administration of rabies vaccines can be used effectively for rabies pre-exposure and post-exposure prophylaxis.

Optimum processing conditions for a trivalent-inactivated bovine viral diarrhea virus (BVDV) vaccine using field strains and immunogenicity of candidate formulations with different adjuvants.

Bovine viral diarrhea virus (BVDV) is among the common bovine pathogens worldwide. One of the prominent protection measures of BVDV is vaccination. This study aimed to determine the growth characteristics, inactivation kinetics of vaccine candidates using local BVDV strains [TR-26 (BVDV-1f), TR-21 (BVDV-1l), and TR-15 (BVDV-2b)], and the serological response in experimental animals to inactivated BVDV vaccine formulations prepared with different adjuvants. Optimum MOI values for BVDV strains TR-26, TR-21, and TR-15 were determined as 0.1, 1.0, and 0.01, respectively. In addition, growth curves of TR-26, TR-21, and TR-15 strains were created, and it was determined that they reached the highest titers at 12, 48, and 36h p.i., respectively. The strains TR-26, TR-21, and TR-15 with titers of 106.5, 106.5, and 105.25 TCID50/ml were completely inactivated by 1 mM binary ethyleneimine (BEI) at the 10th, 16th, and 10th hours of treatment, respectively. Guinea pigs were immunized with four vaccine formulations (F1, F2, F3, F4), two with aluminum-based [Al(OH)3, Al(OH)3+Saponin] and two with oil-based (ISA 50 and ISA 206) adjuvants. Neutralization tests were applied to determine the humoral immune response developed after vaccination. Both homologous and heterologous BVDV strains were used for evaluations. Oil adjuvanted vaccines were more efficient to induce antibody titers compared to Al(OH)3-based vaccines. In addition, between the oil adjuvanted vaccines, the titers of neutralizing antibodies obtained by Montanide® ISA 206 formulation were significantly higher than in Montanide® ISA 50 (p < 0.05). Post-vaccinal neutralizing antibodies were detected in the first sampling at 21st day and lasted longer than a 111 days period. The highest antibody response in Guinea pigs was for the strain TR-15. The availability of using BVDV-lf, 1l, and 2b local strains in vaccines and their effectiveness against homologous and heterologous strains have been demonstrated.

Serologic Response to Hepatitis B Vaccination in People Living with HIV in Cali, Colombia

Introduction: Hepatitis B virus (HBV) and HIV coinfection is common, with reported prevalence of up to 20%. This coinfection is associated with an increased risk of chronicity and complications compared with the general population. HBV vaccination is the cornerstone of prevention; however, people living with HIV (PLWH) exhibit a reduce immune response to the vaccine. The objective of this study was to determine the incidence and factors associated with the lack of seroconversion after HBV vaccination in PLWH in Cali, Colombia. Materials and methods: This was a retrospective cohort study in two HIV outpatient clinics. We included HIV-confirmed adult patients admitted between 2017 and 2020, with no evidence of HBV infection and with under the protective levels of HBV surface antibodies (anti-HBs &lt; 10 IU/ml) on admission, who received at least one dose of HBV vaccine, and had reported anti-HBs post vaccination. The outcome was lack of seroconversion (anti-HBs &lt; 10 IU/ml post vaccination) Results: Of 512 patients screened, 73.8 % (95 % CI: 73.4–74.2) had anti-HBs &lt; 10 IU/ml on admission of whom 224 were included. The incidence of anti-HBs &lt; 10 IU/ml post vaccination was 39.7% (95% CI: 39.5–39.9). Age (aOR 1.03 95% CI: 1-1.05), CD4 count &lt; 200 cells (aOR 7.8 95% CI: 2–29.8), BMI &gt; 30 kg/m2 (aOR 5.1 95% CI: 1.9–14.1), and smoking in females (aOR 6.8 95% CI: 1–81) were risk factors for lack of seroconversion. In contrast, two (aOR 0.2 95% CI: 0.06–0.9) or three (aOR 0.2 95% CI: 0.06–0.6) HBV vaccine doses instead of one were protective. Discussion: A significant proportion of PLWH are eligible for HBV vaccination in Cali. In those who received at least one HBV vaccine dose, the incidence of lack of seroconversion is comparable to reports in Latin America. The factors associated with lack of seroconversion could be considered to adjust the guidelines for HBV vaccination in PLWH in Colombia.

Beyond Suppression: Peripheral T Cell Responses to Vaccination in Inflammatory Bowel Disease Patients Undergoing Anti-Tumor-Necrosis-Factor Therapy.

Alimentary tract inflammation in inflammatory bowel disease (IBD) is treated by systemically administered drugs that alter fundamental host immune responses. Biologics that target tumor necrosis factor (TNF) are first-line biologics in IBD, used widely for their effectiveness, steroid-sparing quality, and lower cost. While they enable a significant proportion of patients to achieve clinical remission, they carry an increased risk of infection and poor serological responses to vaccination. Conversely, our understanding of adaptive T cell responses in anti-TNF-treated IBD patients remains limited. The introduction of COVID-19 vaccines has prompted research that both challenges and refines our view on immunomodulatory therapy and its potential implications for immunity and protection. Here, we review these emergent findings, evaluate how they shape our understanding of vaccine-induced T cell responses in the context of anti-TNF therapy in IBD, and provide a perspective highlighting the need for a holistic evaluation of both cellular and humoral immunity in this population.

Assessment of Antibody Levels and Vaccine-induced Serologic Responses After Completion of Cancer Treatment in Pediatric Patients: A 6-year Experience in Turkey on HAV, HBV, VZV, and MMR Vaccinations

Objective: Childhood cancer treatment disrupts vaccination schedules and weakens or eliminates vaccine-induced immunity. In addition, post-treatment vaccine responses vary. This study aimed to assess post-treatment serum antibody levels and vaccine responses in children. Methods: Pediatric patients treated at Hacettepe University between years 2015 and 2020, achieved remission after chemotherapy for lymphoma and solid tumors were included. Post-treatment vaccination status, serum antibody levels for hepatitis A (HAV), hepatitis B (HBV), varicella-zoster (VZV), measles-mumps-rubella (MMR), and changes in vaccine responses were retrospectively analyzed. Results: The study included 533 patients. Post-treatment seronegativity rates were: measles (83.5%), HAV (64%), rubella (60.1%), HBV (48.5%), VZV (43.3%), and mumps (28%). Post-treatment antibody loss was observed for measles (47.1%), HAV (31.9%), HBV (31.4%), mumps (28.6%), VZV (21.7%), and rubella (11.4%). Seropositivity after 1 vaccine dose was seen with HAV (83.6%), rubella (82.9%), HBV (81.4%), VZV (63.5%), mumps (45.4%), and measles (33.3%). Seropositivity after 2 vaccine doses was achieved with HAV (98.8%), VZV (84.6%), rubella (80%), HBV (80%), measles (32.2%), and mumps (36.2%). Conclusion: Post-treatment serological vaccine responses in children were lower than anticipated despite multiple doses. Given the potential need for periodic serological assessments and booster vaccinations, long-term follow-ups are planned.

Development and Validation of an Indirect and Blocking ELISA for the Serological Diagnosis of African Swine Fever.

African swine fever (ASF) is an economically devastating viral disease of pigs caused by the ASF virus (ASFV). The rapid global spread of ASF has increased the demand for ASF diagnostics to be readily available and accessible. No commercial ASF enzyme-linked immunosorbent assay (ELISA) kits are manufactured and licensed in North America. Here, we report the development of two serological diagnostic assays, a blocking ELISA (bELISA) based on ASFV glycoprotein p54 and an indirect ELISA (iELISA) based on ASFV glycoproteins p54 and p72. The assays showed high sensitivity and specificity and detected anti-ASFV antibodies in serum samples from experimentally infected animals as early as 8 days post-infection. The two assays were produced commercially (AsurDx™ bELISA and iELISA) and subjected to extensive validation. Based on data from a set of characterized reference sera, the prototype commercial assays, while maintaining 100.00% specificity, showed 97.67% (AsurDx™ bELISA) and 83.72% (AsurDx™ iELISA) sensitivity. Both prototype assays detected anti-ASFV antibodies in serum samples collected from pigs experimentally infected with multiple ASFV strains and field samples collected from sick, recovering, and vaccinated animals. The two commercially available assays can be used in routine ASF diagnostics, serological surveys, and for evaluating serological responses to ASF vaccine candidates.

Scrub Typhus Outbreak among Soldiers in Coastal Training Area, Australia, 2022.

A scrub typhus outbreak occurred among 24 soldiers from 2 Australian Defence Force infantry units following separate training events conducted in the same coastal location in tropical North Queensland, Australia, in June 2022. Seven soldiers visited a hospital, 5 requiring admission. Outbreak recognition was hampered by the geographic dispersion of soldiers after the exercise and delayed case identification resulting from such factors as prolonged incubation, cross-reactive serologic responses to other pathogens, the nonspecific symptoms of scrub typhus, and the illness's nonnotifiable status in the state of Queensland. Our investigation focused on personal protective measures in a subanalysis of 41 soldiers, revealing an association between scrub typhus infection and the use of doxycycline chemoprophylaxis and permethrin uniform dipping.

Efficacy and Safety of Tenofovir Amibufenamide and Tenofovir Alafenamide for First-Time HBV-Related Decompensated Cirrhosis.

Clinical studies of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) treatment in patients with HBV-related decompensated cirrhosis (HBV-DC) are limited. This study evaluated the efficacy and safety of TMF versus TAF in naive-treated patients with first-time HBV-DC. Based on the antiviral drug used, patients were categorised into the TMF group and the TAF group. Virological and serological responses, hepatic and renal functions and blood lipid changes in both groups were evaluated during 48 weeks of treatment. A total of 98 patients were enrolled, 45 in the TMF group and 53 in the TAF group. At 48 weeks of treatment, the proportions of patients who achieved complete virological response (CVR) were 85.7% and 90.7%, respectively (p = 0.791). Improvement of at least 2 points in Child-Turcotte-Pugh scores was observed in 64.3% versus 79.1% (p = 0.169) of the patients. There were no significant changes in serum creatinine, estimated glomerular filtration rate or total cholesterol from baseline to week 48 between the two groups. Cystatin C remained stable in the TMF group but increased over time in the TAF group (p < 0.001). Low-density lipoprotein cholesterol remained stable in the TMF group but increased significantly in the TAF group at week 48 (p = 0.015). These results suggest that both TMF and TAF can rapidly suppress HBV replication, improve hepatic function and have no negative effects on renal function among patients with HBV-DC. Regarding lipid metabolism, both showed a better safety, while regular monitoring of blood lipid levels is recommended.

Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis.

Population surveillance studies of serum-neutralizing activity against RSV are crucial for evaluating RSV vaccine efficacy and vulnerabilities to new strains. Here, we designed and validated a high-throughput assay for assessing anti-RSV neutralizing activity, standardized its measurements for comparison with other methodologies, and demonstrated its applicability to real-world samples. Our assay is precise, linear, and yields measurements consistent with other standardized assays, offering a methodology useful for large-scale studies of RSV immunity. We also find no significant difference in neutralizing titers among adults between those taken before and after large RSV outbreaks associated with the latter stages of the coronavirus disease of 2019 (COVID-19) public health emergency, underlining the need for a greater understanding of the dynamics of serological responses to RSV infection.

Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma

PurposeDespite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable.MethodsA retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.ResultsThe rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor.ConclusionIn pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

Proteomic approach to identify host cell attachment proteins provides protective Pseudomonas aeruginosa vaccine antigen FtsZ

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes severe nosocomial infections in susceptible individuals due to the emergence of multidrug-resistant strains. There are no approved vaccines against P. aeruginosa infections nor candidates in active clinical development, highlighting the need for novel candidates and strategies. Using a cell-blot proteomic approach, we reproducibly identified 49 proteins involved in interactions with human lung epithelial cells across four P. aeruginosa strains. Among these were cell division protein FtsZ and outer membrane protein OpmH. Escherichia coli BL21 cells overexpressing recombinant FtsZ or rOpmH showed a 66- and 15-fold increased ability to attach to 16HBE14o− cells, further supporting their involvement in host cell attachment. Both antigens led to proliferation of NK and CD8+ cytotoxic T cells, significant increases in the production of IFN-γ, IL-17A, TNF and IL-4 in immunised mice and elicited strong antigen-specific serological IgG1 and IgG2c responses. Immunisation with FtsZ significantly reduced bacterial burden in the lungs by 1.9-log CFU and dissemination to spleen by 1.8-log CFU. The protective antigen candidate, FtsZ, would not have been identified by traditional approaches relying on either virulence mechanisms or sequence-based predictions, opening new avenues in the development of an anti-P. aeruginosa vaccine.

B cell expression of the enzyme PexRAP, an intermediary in ether lipid biosynthesis, promotes antibody responses and germinal center size.

The qualities of antibody (Ab) responses provided by B lymphocytes and their plasma cell (PC) descendants are crucial facets of responses to vaccines and microbes. Metabolic processes and products regulate aspects of B cell proliferation and differentiation into germinal center (GC) and PC states as well as Ab diversification. However, there is little information about lymphoid cell-intrinsic functions of enzymes that mediate ether lipid biosynthesis, including a major class of membrane phospholipids. Imaging mass spectrometry (IMS) results had indicated that concentrations of a number of these phospholipids were substantially enhanced in GC compared to the background average in spleens. However, it was not clear if biosynthesis in B cells was a basis for this finding, or whether such cell-intrinsic biosynthesis contributes to B cell physiology or Ab responses. Ether lipid biosynthesis can involve the enzyme PexRAP, the product of the Dhrs7b gene. Using combinations of IMS and immunization experiments in mouse models with inducible Dhrs7b loss-of-function, we now show that B lineage-intrinsic expression of PexRAP promotes the magnitude and affinity maturation of a serological response. Moreover, the data revealed a Dhrs7b -dependent increase in ether phospholipids in primary follicles with a more prominent increase in GC. Mechanistically, PexRAP impacted B cell proliferation via enhanced survival associated with controlling levels of ROS and membrane peroxidation. These findings reveal a vital role of this peroxisomal enzyme in B cell homeostasis and the physiology of humoral immunity.

Analysis of Powassan Virus Genome Sequences from Human Cases Reveals Substantial Genetic Diversity with Implications for Molecular Assay Development.

Powassan virus (POWV) is an emerging tick-borne virus that causes severe meningoencephalitis in the United States, Canada, and Russia. Serology is generally the preferred diagnostic modality, but PCR on cerebrospinal fluid, blood, or urine has an important role, particularly in immunocompromised patients who are unable to mount a serologic response. Although the perceived poor sensitivity of PCR in the general population may be due to the biology of infection and health-seeking behavior (with short viremic periods that end before hospital presentation), limitations in assay design may also contribute. Genome sequences from clinical POWV cases are extremely scarce; PCR assay design has been informed by those available, but the numbers are limited. Larger numbers of genome sequences from tick-derived POWV are available, but it is not known if POWV genomes from human infections broadly mirror genomes from tick hosts, or if human infections are caused by a subset of more virulent strains. We obtained viral genomic data from 10 previously unpublished POWV human infections and showed that they broadly mirror the diversity of genome sequences seen in ticks, including all three major clades (lineage I, lineage II Northeast, and lineage II Midwest). These newly published clinical POWV genome sequences include the first confirmed lineage I infection in the United States, highlighting the relevance of all clades in human disease. An in silico analysis of published POWV PCR assays shows that many assays were optimized against a single clade and have mismatches that may affect their sensitivity when applied across clades. This analysis serves as a launching point for improved PCR design for clinical diagnostics and environmental surveillance.

Seroprevalence of SARS-CoV-2 antibodies among healthy blood donors: a systematic review and meta-analysis

IntroductionThe development of a potent immune response and antibodies against SARS-CoV-2 is important for herd immunity. The serological response may be due to a previous infection or vaccination. Healthy blood donors could represent and provide information on the immune status of the general population. Therefore, we estimated the global and regional prevalence of SARS-CoV-2 antibodies among healthy blood donors.MethodsWe conducted a systematic search of PubMed, Scopus, and ProQuest from December 2019 to January 2023. After critical appraisal and quality assessment, a qualitative synthesis of the identified relevant articles was performed. The random-effects model was used to estimate the pooled prevalence of SARS-CoV-2 antibodies. Funnel plots and Egger’s test were used to assess publication bias. Sensitivity analysis was performed, and heterogeneity was quantified using I2 statistics.ResultsA total of 70 peer-reviewed articles were selected that together included 2,454,192 blood donors. The global estimated pooled prevalence of SARS-CoV-2 antibodies among healthy blood donors was 10.3% (95% CI: 4.6 – 18.0%, n = 70). The highest seroprevalence was observed in Asia (17.7%), followed by Africa (16.1%). The seroprevalence in studies conducted before the introduction of the vaccine was 6.1%, whereas those of studies conducted after vaccines were available was 27.6%. High seroprevalence was observed in studies that measured antibodies against the S protein of the virus (15.2%), while lower (12.5%) in those that measured antibodies against the N protein. A high seroprevalence was observed in studies that only measured IgG antibodies (16.3%), and it was 5.9% in studies that measured total antibodies.ConclusionThe prevalence of SARS-CoV-2 antibodies among healthy blood donors varies, potentially indicating geographical disparities in transmission and vaccination rates. To enhance community resilience, addressing these differences through inclusive health policies and adaptable public health measures is crucial.

Triton X-100-treated virus-based ELLA demonstrates discordant antigenic evolution of influenza B virus hemagglutinin and neuraminidase.

Neuraminidase (NA)-specific antibodies have been associated with protection against influenza and thus NA is considered a promising target for next-generation vaccines against influenza A (IAV) and B viruses (IBV). NA inhibition (NI) by antibodies is typically assessed using an enzyme-linked lectin assay (ELLA). However, ELLA can be confounded by anti-hemagglutinin (anti-HA) antibodies that block NA by steric hindrance (termed HA interference). Although strategies have been employed to overcome HA interference for IAV, similar approaches have not been assessed for IBV. We found that HA interference is common in ELLA using IBV, rendering the technique unreliable. Anti-HA antibodies were not completely depleted from sera by HA-expressing cell lines, and this approach was of limited utility. In contrast, we find that treatment of virions with Triton X-100, but not Tween-20 or ether, efficiently separates the HA and NA components and overcomes interference caused by anti-HA antibodies. We also characterize a panel of recombinant IBV NA proteins that further validated the results from Triton X-100-treated virus-based ELLA. Using these reagents and assays, we demonstrate discordant antigenic evolution between IBV NA and HA over the last 80 years. This optimized ELLA protocol will facilitate further in-depth serological surveys of IBV immunity as well as antigenic characterization of the IBV NA on a larger scale.IMPORTANCEInfluenza B viruses (IBVs) contribute to annual epidemics and may cause severe disease, especially in children. Consequently, several approaches are being explored to improve vaccine efficacy, including the addition of neuraminidase (NA). Antigen selection and assessment of serological responses will require a reliable serological assay to specifically quantify NA inhibition (NI). Although such assays have been assessed for influenza A viruses (IAVs), this has not been done of influenza B viruses. Our study identifies a readily applicable strategy to measure the inhibitory activity of neuraminidase-specific antibodies against influenza B virus without interference from anti-hemagglutinin (anti-HA) antibodies. This will aid broader serological assessment of influenza B virus-specific antibodies and antigenic characterization of the influenza B virus neuraminidase.

Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease.

Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn's disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.