Serological Response Research Articles

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.

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.

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.

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.

Smoking and serological response to influenza vaccine

ABSTRACT Cigarette smoking confers additional risk from influenza. This study assessed the effect of smoking on humoral immune response to influenza vaccine. Adults ≥50 y of age were enrolled during the 2011–2016 influenza vaccination seasons in an observational prospective study. Non-fasting whole blood samples for hemagglutination inhibition (HAI) assays were obtained from participants at pre- and 28 d post-clinically administered, trivalent influenza vaccination. Among 273 participants, 133 subjects self-reported as never smokers, 87 as ex-smokers, and 53 as current smokers. Postvaccination geometric mean HAI titers were significantly higher among smokers for A/H1N1 (p = .031) and A/H3N2 (p = .001). Relative to never smokers, smoking was independently related to seroconversion to A/H1N1, A/H3N2 and B. The adjusted odd ratios (ORs) were 5.2 [95% confidence interval (CI), 2.3, 11.5] for seroconversion to A/H1N1, 5.4 (95% CI, 2.4, 12.1) for A/H3N2, and 2.7 (95% CI, 1.3, 5.7) for B. Smoking was also independently related to seroprotection to A/H1N1, A/H3N2 and B. The ORs were 3.6 (95% CI, 1.6, 8.08) for seroprotection to A/H1N1 in smokers, 2.7 (95% CI, 1.14, 6.5) for A/H3N2, and 2.5 (95% CI, 1.1, 5.7) for B. Although the mechanism is unclear, smokers showed a better immune response to influenza vaccination than never smokers and ex-smokers. The results can be used to emphasize the value of influenza vaccination for smokers.

Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections.

Rising incidence of invasive beta-haemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated. A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE or GBS. Antibody responses to six Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2log10 arbitrary units/mL (AU/mL). Sixty-seven participants were enrolled. Thirty-three participants were included in the final analysis (12, 11 and 10 with Strep A, SDSE and GBS, respectively). The median serological response for participants with Strep A was significant for all tested antigens (median >0.2log10 difference between acute and convalescent samples; P<0.05 for all). Those with SDSE had comparable and significant median (IQR) responses to streptolysin-O (0.65 [0.36-1.67], P=0.004), S. pyogenes adhesion and division protein (0.68 [0.36-1.63], P=0.005) and C5a peptidase (ScpA; 0.30 [0.23-1.06]), P=0.004). GBS responses were limited to ScpA only (0.34 [0.08-0.52], P=0.05). Patients with invasive Strep A infection mount robust antibody responses to six non-M protein vaccine candidate antigens. Similar significant responses to C5a peptidase in those with invasive SDSE and GBS infection highlight the importance of further research into cross-species protection and immunological correlates of vaccine efficacy.

Serum metabonomics reveal the effectiveness of human placental mesenchymal stem cell therapy for primary sclerosing cholangitis.

The metabolic patterns of human placental-derived mesenchymal stem cell (hP-MSC) treatment for primary sclerosing cholangitis (PSC) remain unclear, and therapeutic effects significantly vary due to individual differences. Therefore, it is crucial to investigate the serological response to hP-MSC transplantation through small molecular metabolites and identify easily detectable markers for efficacy evaluation. Using Mdr2-/- mice as a PSC model and Mdr2+/+ mice as controls, the efficacy of hP-MSC treatment was assessed based on liver pathology, liver enzymes, and inflammatory factors. Serum samples were collected for 12C-/13C-dansylation and DmPA labeling LC-MS analysis to investigate changes in metabolic pathways after hP-MSC treatment. Key metabolites and regulatory enzymes were validated by qRT-PCR and Western blotting. Potential biomarkers of hP-MSC efficacy were identified through correlation analysis and machine learning. Collectively, the results of the liver histology, serum liver enzyme levels, and inflammatory factors supported the therapeutic efficacy of hP-MSC treatment. Based on significant differences, 41 differentially expressed metabolites were initially identified; these were enriched in bile acid, lipid, and hydroxyproline metabolism. After treatment, bile acid transport was accelerated, whereas bile acid production was reduced; unsaturated fatty acid synthesis was upregulated overall, with increased FADS2 and elongase expression and enhanced fatty acid β-oxidation; hepatic proline 4-hydroxylase expression was decreased, leading to reduced hydroxyproline production. Correlation analysis of liver enzymes and metabolites, combined with time trends, identified eight potential biomarkers: 2-aminomuconate semialdehyde, L-1-pyrroline-3-hydroxy-5-carboxylic acid, L-isoglutamine, and maleamic acid were more abundant in model mice but decreased after hP-MSC treatment. Conversely, 15-methylpalmitic, eicosenoic, nonadecanoic, and octadecanoic acids were less abundant in model mice but increased after hP-MSC treatment. This study revealed metabolic regulatory changes in PSC model mice after hP-MSC treatment and identified eight promising biomarkers, providing preclinical evidence to support therapeutic applications of hP-MSC.

Clustering Analysis Identified Distinct Clinical Phenotypes among Hemodialysis Patients in Their Immunological Response to the BNT162b2 mRNA Vaccine against SARS-CoV-2.

Background: The 2019 coronavirus disease (COVID-19) pandemic induced a major health crisis worldwide, notably among end-stage kidney disease (ESKD) patients. Vaccination against SARS-CoV-2, especially with messenger RNA (mRNA) vaccines, is highly effective and reduces hospitalization and mortality in both the general and ESKD populations. Age and previous COVID-19 infection have been identified as major determinants of the vaccine response in both the general population and ESKD patients. Methods: To determine the specific phenotype of ESKD patients in relation to their vaccine response, a clustering approach was used in a cohort of 117 fully vaccinated patients. Results: Clustering revealed three distinct clinical phenotypes among hemodialysis patients in terms of immunological response. Two clusters, consisting of either women with a long dialysis history or male subjects with diabetes with a moderate history of dialysis, exhibited low levels of IgG anti-spike antibodies. The third cluster consisted of non-diabetic middle-aged men with a moderate dialysis vintage and a very good serological response to vaccination. Conclusions: These vaccinal phenotypes of dialysis patients are easily identifiable in current practice, allowing for differential serological follow-up and tailored booster SARS-CoV-2 vaccination.

Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials.

In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Here, we report the studies' final 8-year results. CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Among 1298 patients randomised to double-blind TAF (n = 866) or double-blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing-equals-failure analysis) and 95%, 94% and 97% (missing-equals-excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft-Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double-blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. gov numbers NCT01940341 and NCT01940471.

Potential Association between Shift Work and Serologic Response to Hepatitis B Vaccination among Manufacturing Workers in Republic of Korea.

(1) Background: Shift work can affect physical health and the immune system by altering the body's circadian rhythms. This study investigated the factors associated with the hepatitis B virus (HBV) vaccination response in manufacturing workers, classified by whether they engaged in shift work or not. (2) Methods: This retrospective observational study was conducted among adults employed at two manufacturing companies. Those with negative initial hepatitis B surface antibody (HBsAb) levels before vaccination and who subsequently received a three-dose series of HBV vaccine were enrolled. Hepatitis B surface antibodies were examined for 3 years after the first dose. The endpoint of this study was the failure of a seroprotective anti-HB response after vaccination (HBsAb < 10 mIU/mL). Binary logistic regression models were used to analyze factors associated with response failures. (3) Results: Of the 1103 eligible subjects, 337 (30.6%) were shift workers. The failure rate was numerically higher in the shift workers (9.2%) than in the non-shift workers (7.9%), without statistical significance (p = 0.405). However, after adjustment with the binary logistic regression models, the shift workers had a statistically significantly higher rate of response failures than the non-shift workers (odds ratio 2.87; 95% confidence interval 1.64-5.05, p < 0.001), as did males, older workers, those with a low initial anti-HB titer, those with a vitamin D deficiency, and current smokers. (4) Conclusions: Our findings suggest a possible association between shift work and the serologic responses to HBV vaccination. Novel strategies for vaccination should be considered for shift workers.

Chitosan siRNA Nanoparticles Produce Significant Non-Toxic Functional Gene Silencing in Kidney Cortices.

Chitosan shows effective nucleic acid delivery. To understand the influence of chitosan's molecular weight, dose, payload, and hyaluronic acid coating on in vivo toxicity, immune stimulation, biodistribution and efficacy, precisely characterized chitosans were formulated with unmodified or chemically modified siRNA to control for innate immune stimulation. The hemocompatibility, cytokine induction, hematological and serological responses were assessed. Body weight, clinical signs, in vivo biodistribution and functional target knockdown were monitored. Hemolysis was found to be dose- and MW-dependent with the HA coating abrogating hemolysis. Compared to cationic lipid nanoparticles, uncoated and HA-coated chitosan nanoparticles did not induce immune stimulation or hematologic toxicity. Liver and kidney biomarkers remained unchanged with chitosan formulations, while high doses of cationic lipid nanoparticles led to increased transaminase levels and a decrease in body weight. Uncoated and HA-coated nanoparticles accumulated in kidneys with functional knockdown for uncoated chitosan formulations reaching 60%, suggesting potential applications in the treatment of kidney diseases.

Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients

ABSTRACTIntroductionHepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients.MethodsWe conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb &lt; 10 IU/L) at 30 days posttransplantation (D30).ResultsAmong 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p &lt; 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p &lt; 0.001).ConclusionsAlthough less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

Immunostimulating effect of inactivated Parapoxvirus ovis on the serological response to equine influenza booster vaccination

Immunostimulating effect of inactivated <i>Parapoxvirus ovis</i> on the serological response to equine influenza booster vaccination

Serological responses of horses in response to vaccination in a farm associated with a natural outbreak of strangles

Serological responses of horses in response to vaccination in a farm associated with a natural outbreak of strangles