Search Results (1,552)

This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in IBD were also explored. A total of 86 UC patients, 68 CD patients, and 41 healthy controls were prospectively enrolled from four Norwegian hospitals (2013–2022). Diagnosis and disease activity were established using standard clinical, endoscopic, and biomarker criteria. Serum samples were analyzed for total Ig, IgG, IgM, IgA, and IgE antibodies against A. simplex and Pseudoterranova decipiens using ELISA. Anti-A. simplex IgG seroprevalence was 4.9% in controls and 3.2% in IBD (3.5% UC, 2.9% CD). IgM seroprevalence was 0% in all groups. IgA seroprevalence was higher in IBD (16.2%) than controls (4.9%), with 14.0% in UC and 19.1% in CD. IgE seroprevalence was low across all groups. Smoking correlated with lower antibody levels and higher surgery rates. In UC, higher anti-A. simplex IgG and IgE levels were associated with milder disease and better prognosis. Anti-TNFα and azathioprine treatments were linked to higher anti-A. simplex IgA. Norwegian UC and CD patients had significantly higher anti-A. simplex total Ig and IgA seroprevalence than healthy controls, indicating increased exposure or immune response. Anti-A. simplex IgG and IgE may serve as markers of clinical activity in UC. Further research is warranted to clarify the clinical significance of these findings. Full article

Background: This study aimed to assess the prevalence of SARS-CoV-2 infection, vaccination, and immune status among a population, both Dentists and University Professors, within a clinical setting at one and at 12 months after COVID-19 vaccination. Methods: A cross-sectional study involving 47 professionals (aged 27–52) was conducted in the University Fernando Pessoa. Participants completed an online survey on SARS-CoV-2 infection status and vaccination, received and provided plasma samples for serological analysis. The protocol was approved by the UFP-Ethics Committee. Anti-S1-RBD SARS-CoV-2 IgM and IgG antibody titration values (AU/mL) were measured, by enzyme-linked-immunosorbent assay (ELISA), with reactive immunoglobulins (Ig) seropositivity for values ≥1 AU/mL. Results: SARS-CoV-2 infection rate increased from 8.5% in July 2021 to 48.9% in June 2022, with 8.5% experiencing reinfection. Vaccination rate was 91.5% by July 2021 and increased slightly to 93.6% by June 2022; 72.3% of the sample received a third dose. IgG seropositivity increased from 91.5% to 95.7% in June 2022. After one-year, significant associations were found between IgG seropositivity and both participant’s age (p = 0.009; <50 years) and vaccine doses (p = 0.003; 1–3 doses) received. Conclusions: SARS-CoV-2 infection rate, vaccination, and IgG seropositivity rates were high and increased over one year. The age and vaccination status were associated with the immunity status at 12th month follow-up. Findings highlight variability in IgG seroprevalence due to multiple influencing factors, which justifies future studies. Full article

Bisphenol A (BPA) is an endocrine-disrupting chemical with estrogen-like activity, known to impair immune function. BPA may act as a pro-inflammatory agent, reducing immune response efficacy, increasing bacterial load in E. coli infections, and altering immune responses in parasitic infections (Leishmania major, Nippostrongylus brasiliensis, Toxocara canis) through cytokine and regulatory T-cell modulation. Following its ban in food contact materials in Europe, several analogs have been introduced. This study assessed the immunotoxicity of BPA and six analogs, namely BPAP, BPE, BPP, BPS-MAE, BPZ, and TCBPA, by evaluating in vitro the antibody production. Peripheral blood mononuclear cells from healthy male and female donors were exposed to increasing concentrations of each compound for 24 h. After stimulation with rhIL-2 and ODN2006, IgM and IgG secretion were measured on day six. All compounds suppressed antibody production in a concentration-dependent manner, with some sex-related differences. IC₅₀ values showed BPP as the most potent suppressor, and BPE as the weakest. Similarly, IC₂₀ values confirmed these differences in potency, except for BPA being the weakest for IgM in males. Overall, te results do not support the idea that BPA analogs are safer than BPA. Full article

Background: Understanding the duration and quality of immune memory following SARS-CoV-2 infection and vaccination is critical for informing public health strategies and vaccine development. While waning antibody levels have raised concerns about long-term protection, the persistence of memory B cells (MBCs) and T cells plays a vital role in sustaining immunity. Materials and Methods: We conducted a longitudinal prospective study over 12 months, enrolling 285 participants in total, either after natural infection or vaccination with BNT162b2 or mRNA-1273. Peripheral blood samples were collected at four defined time points (baseline, 1–2 months, 6–7 months, and 12–13 months after vaccination or disease onset). Immune responses were assessed through serological assays quantifying anti-RBD IgG and neutralizing antibodies, B-ELISPOT, and multiparameter flow cytometry for S1-specific memory B cells. Results: Both mRNA vaccines induced robust B cell and antibody responses, exceeding those observed after natural infection. Memory B cell frequencies peaked at 6 months and declined by 12 months, but remained above the baseline. The mRNA-1273 vaccine elicited stronger and more durable humoral and memory B-cell-mediated immunity compared to BNT162b2, likely influenced by its higher mRNA dose and longer prime-boost interval. Class-switched memory B cells and S1-specific B cells were significantly expanded in vaccine recipients. Natural infection induced more heterogeneous immune memory. Conclusions: Both mRNA vaccination and natural SARS-CoV-2 infection induce a comparable expansion of memory B cell subsets, reflecting a consistent pattern of humoral immune responses across all studied groups. These findings highlight the importance of vaccination in generating sustained immunological memory and suggest that the vaccine platform and dosage influence the magnitude and durability of immune responses against SARS-CoV-2. Full article

Hepatitis E virus (HEV) poses a significant public health concern, particularly among immunocompromised populations. This study aimed to investigate HEV seroprevalence, clinical characteristics, and associated risk factors in people living with HIV (PLWH) in Shanghai, China. A retrospective analysis was conducted on serum IgG and IgM antibodies specific to HEV in 670 PLWH and 464 HIV-negative health-check attendees. The overall anti-HEV seropositivity rate among PLWH was 30.15% (202/670, 95% CI 26.68–33.62), with an IgG positivity rate of 30.00% (201/670, 95% CI 26.53–33.47). IgM positivity was observed in 1.19% (8/670, 95% CI 0.59–2.39) of PLWH, and dual IgM/IgG positivity was observed in 1.04% (7/670, 95% CI 0.50–2.16) of PLWH. The seropositivity rate of anti-HEV IgG in the HIV-negative health-check attendees was 17.67% (82/464, 95% confidence interval: 14.20–21.14), with no IgM positivity, which was significantly lower than that in PLWH (χ² = 22.84, p < 0.001). Univariate and multivariate analyses identified advanced World Health Organization (WHO) HIV stage (III/IV) as an independent risk factor for HEV co-infection (p < 0.05). Notably, no significant associations were observed with age, gender, CD4 count, or liver function parameters. These findings underscore the importance of implementing HEV screening protocols and developing targeted preventive strategies for PLWH. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: Rickettsioses are diseases caused by obligate intracellular non-motile coccobacilli transmitted via arthropods. The most common rickettsioses are scrub typhus (ST), typhus group rickettsioses (TGR), and spotted fever group rickettsioses (SFGR). This study aims to provide information and insight into rickettsioses seropositivity among suspected patients in East and Peninsular Malaysia over a six-year period from 2016 to 2021. Methodology/Principal Findings: Data obtained from four state hospitals and one national research institute providing rickettsial serological testing were analyzed using the IBM SPSS (Statistical Package for the Social Sciences) software program. The six-year analysis revealed that ST had the highest number of seropositivity cases, followed by TGR, and SFGR, for both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Of the 3228 samples, 21.6%, 16.1%, and 13.9% of suspected patients were IgM seropositive for ST, TGR, and SFGR, respectively. IgG seropositivity for ST was 21.9%, followed by TGR at 21.4%, and SFGR at 17.2% among suspected rickettsioses cases. All regions in Malaysia were significantly associated with IgM seropositivity for ST, TGR, and SFGR. IgM seropositivity for SFGR was significantly higher in females. Age group 41–65 years was highly associated with IgG seropositivity for ST, TGR, and SFGR. Conclusions/Significance: Analysis of six-year data on ST, TGR, and SFGR seropositivity in Malaysia revealed variations across regions, age groups, and genders. This seropositivity study underscores ST, TGR, and SFGR as possible causes of acute febrile illness among patients suspected of rickettsial disease in Malaysia. The findings contributed to the awareness of reemerging rickettsioses and warrant public health interventions that may reduce the incidence of rickettsioses in Malaysia. Abstract summary: Scrub typhus (ST), typhus group rickettsioses (TGR), and spotted fever group rickettsioses (SFGR) are significant global public health concerns. Our results showed that the highest number of IgM and IgG seropositivity cases was observed for ST, followed by TGR and SFGR. All regions in Malaysia were significantly associated with IgM seropositivity for ST, TGR, and SFGR. East Malaysia exhibited significantly higher seropositivity for ST, TGR, and SFGR than other regions in Malaysia. IgM seropositivity for SFGR was significantly higher in females. The age group 41–65 years was highly associated with IgG seropositivity for ST, TGR, and SFGR. This study highlights the value of serological data in uncovering the hidden burden of disease in Malaysia. In addition, the findings contributed to bridging knowledge gaps on the limited data from Malaysia spanning extended periods, despite being one of the countries in the endemic Tsutsugamushi Triangle. The findings from this study may direct future research on rickettsioses and warrant public health interventions in Malaysia. Full article

Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established clinical manifestations, as it can profoundly affect placental histomorphology. This study aimed to compare T. pallidum-exposed placental villi structures with healthy placentae at term to evaluate the histomorphological differences using stereology. In this case-control study conducted at term (38 weeks ± 2 weeks), 78 placentae were collected from the hospital delivery suites, comprising 39 cases (T. pallidum-exposed) and 39 controls (non-exposed), who were gestational age-matched with other potential confounders excluded. Blood samples from the umbilical vein and placental basal plate were tested for syphilis, using rapid diagnostic test (RDT) kits for T. pallidum (TP) antibodies (IgG and IgM) to classify placentae as exposed to T. pallidum (cases) and non-exposed (controls). Tissue sections were prepared and stained with haematoxylin and eosin, and the mean volume densities of syncytial knots, foetal capillaries, syncytial denuded areas, and intervillous spaces were estimated using stereological methods. Statistical analysis was performed to compare the mean values between the case and control groups. Stereological assessment revealed significant differences between the T. pallidum-exposed and non-exposed groups with regard to syncytial knots (p < 0.0001), syncytial denudation (p < 0.0001), and foetal capillaries (p < 0.0001), but no significant difference in the intervillous space was found (p = 0.1592). Therefore, our study shows, for the first time, that the histomorphology of human placental villi appears to be altered by exposure to T. pallidum. It will, therefore, be interesting to determine whether these changes in the placental villi translate into long-term effects on the baby. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization assays. However, B cell-mediated responses are not assessed in these assays. B cells are professional antigen-presenting cells (APCs) and secrete antibodies toward immunogenic mAbs. Therefore, methods to determine B cell responses would be beneficial for immunogenicity risk prediction and may provide a more comprehensive assessment of risk. Methods: We used a PBMC culture method with the addition of IL-4, IL-21, B cell activating factor (BAFF), and an anti-CD40 agonist mAb to support B cell survival and activation. Results: B cells in this assay format become activated, proliferate, and secrete IgG. A panel of 51 antibodies with varying clinical immunogenicity rates were screened in this assay with IgG secretion used as a readout for immunogenicity risk. IgG secretion differed among test articles but did not correlate with the clinical immunogenicity rating. Conclusions: This dataset highlights the challenges of developing a B cell assay for immunogenicity risk prediction and provides a framework for further refinement of a B cell-based assay for immunogenicity risk prediction of mAbs. Full article

Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELD^TM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: Healthy adults over 18 years of age received two injections of ECV-19 or CS vaccines, with 4 weeks between prime and boost. Analysis was carried out in individuals with immunogenicity measurements available at all 4 timepoints (weeks 0, 6, 30, and 56; n = 535 for ECV-19 and n = 260 for CS). Results: 2 weeks after boosting (week 6), ECV-19 elicited higher median anti-RBD IgG (1512 vs. 340 BAU/mL, p < 0.001) and neutralizing antibodies (1280 vs. 453 median microneutralization (MN) titer, p < 0.001) compared to CS. Anti-RBD IgG remained higher for ECV-19 compared to CS through week 30 (412 vs. 238 BAU/mL, p < 0.001) and 56 (425 vs. 260 BAU/mL, p < 0.001). MN titers remained higher for ECV-19 compared to CS through week 30 (640 vs. 453, p < 0.001) and 56 (453 vs. 320, p < 0.001). Correlation between anti-RBD IgG and neutralization titers persisted throughout the study. Women generally exhibited greater antibody responses than men. In the first six months following immunization, the ECV-19 group had a median antibody half-life of 80 days for anti-RBD IgG and 112 days for MN titer. In the subsequent six months, antibody half-life increased to 237 days for anti-RBD IgG and 168 days for MN titer. Conclusions: Following initial prime-boost vaccination, ECV-19 maintained higher anti-RBD IgG and neutralizing antibody titers relative to the CS comparator over a full-year period. Full article

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection. Full article

Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3⁺ T cell frequencies, especially CD3^+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3⁺. All treatments diminished CD19⁺/IL-10⁺ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression. Full article

Background: Measuring frequencies of antigen-specific memory B cells (B_mem), their immunoglobulin (Ig) class and subclass usage, cross-reactivity, and affinity can provide insights into the efficacy of future antibody responses in case of antigen re-encounter. B cell ImmunoSpot^® assays can provide such information; however, like most cell-based tests, they require considerable amounts of blood to be drawn from the donor and this has hindered their inclusion in clinical trials and routine immune diagnostics. Methods: We introduce strategies for reducing the cell numbers required to 2–3 million peripheral blood mononuclear cells (PBMCs) per antigen, obtainable from 2–3 mL of blood from healthy adult donors. Results: Except when B_mem frequencies were very low, we found that testing PBMCs in singlet wells, but in serial dilution, enables as reliable B_mem frequency assessments as when testing replicate wells at a single fixed cell number. Additionally, B cell ImmunoSpot^® assays can be multiplexed for detecting four Ig classes, or IgG subclasses, simultaneously and without loss of sensitivity. The requirement for low cell numbers and the retention of B cell functionality by cryopreserved PBMCs equivalent to freshly isolated material implies that fewer than the standard 10 million PBMCs per vial can be frozen. This would reduce the number of individuals who could not be tested for B_mem due to insufficient availability of PBMCs, a common problem with such assays. Conclusions: The predictable need for and recovery of cryopreserved PBMCs facilitates planning of and optimal cell utilization in B cell ImmunoSpot^® assays and increases the practical feasibility of extensive B_mem characterization in larger cohorts. Full article

The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD^® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection. Full article