Search Results (259)

Background/Objectives: Typically, studies aiming to assess the ability of canine parvovirus (CPV) vaccines to immunise puppies with maternally derived antibody (MDA) are undertaken using group-housed puppies. Since live attenuated vaccine virus is invariably shed in the faeces, this can result in repeated oral re-exposure and puppies which failed to respond to the initial vaccination may respond instead to shed vaccine virus in the environment, thus artificially enhancing the efficacy of the vaccine. This problem can be avoided by adopting a pair-housed study design where one vaccinated pup is housed with one unvaccinated sentinel. Using this design, we examine the capability of four commercially available canine parvovirus vaccines to immunise MDA-positive pups. Methods: Thirty-four 6-week-old puppies born to vaccinated dams were divided into four vaccine groups with similar MDA ranges. Within each group puppies were paired based on matching MDA titres, and each pair was housed in separate biocontainment accommodation. In each pair, the pup with the highest MDA was vaccinated and the other left as an unvaccinated sentinel. All vaccinates were given a single dose of one of the vaccines. Vaccinates and sentinels were then bled every 2–4 days and CPV antibody was measured. Daily rectal swabs were also collected from all pups to identify any shed vaccinal CPV. Results: All the pups vaccinated with Nobivac DP PLUS seroconverted, with significantly higher antibody titres compared to the pups in other vaccine groups, all shed vaccine virus, and all bar one of the sentinel pups seroconverted. In the other groups, only vaccinated pups with lower levels of MDA seroconverted and shed vaccine virus but none of the sentinel pups seroconverted. Conclusions: Different canine parvovirus vaccines differ in their ability to replicate in and immunise puppies with MDA, the levels of which may vary widely between individuals. The shedding of vaccinal CPV is an important consideration when designing studies to demonstrate efficacy in MDA-positive puppies. Full article

Background: Antinuclear antibodies (ANAs) serve as crucial biomarkers for diagnosing systemic autoimmune diseases; however, their interpretation can be complex and may not always correlate with clinical symptoms. Methods: A comprehensive narrative review was conducted to evaluate the peer-reviewed literature published between 1961 and 2025. Databases, including PubMed and Scopus, were searched using combinations of controlled vocabulary and free-text terms relating to antinuclear antibodies and their clinical significance. The objective was to gather and synthesize information regarding the diagnostic utility and interpretation of ANA testing in routine medical practice. Discussion: The indirect immunofluorescence assay (IIF) on HEp-2 cells is established as the gold standard for detecting ANAs, facilitating the classification of various fluorescent patterns. While a positive ANA test can suggest autoimmune disorders, the presence and titre must be interpreted alongside clinical findings, as low titres often lack diagnostic significance. Findings indicate that titres higher than 1:160 may provide greater specificity in differentiating true positives from false positives in healthy individuals. The study also emphasizes the relevance of fluorescence patterns, with specific patterns linked to particular diseases, although many do not have strong clinical correlations. Moreover, certain autoantibodies demonstrate high specificity for diseases like systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Ultimately, while ANA testing is invaluable for diagnosing connective tissue diseases, healthcare providers must consider its limitations to avoid misdiagnosis and unnecessary treatment. Conclusions: ANA testing is a valuable tool in the diagnosis of connective tissue diseases, but its interpretation must be approached with caution. Clinical context remains crucial when evaluating ANA results to avoid misdiagnosis and overtreatment. This review is about the diagnostic aspects and clinical consequences of ANA testing, as well as highlighting both the diagnostic benefits and the potential limitations of this procedure in everyday clinical practice. The review fills a gap in the literature by integrating the diagnostic and clinical aspects of ANA testing, with a focus on real-world interpretation challenges. Full article

Background: Despite the widespread implementation of childhood vaccination programmes, hepatitis B virus (HBV) infection remains an ongoing occupational risk for healthcare students. In multi-ethnic and international university settings, differences in vaccination programmes and immune responses must be considered. This retrospective study aimed to assess the prevalence of protective levels of anti-HBs among medical students at an international university in Rome, exploring associations with demographic and vaccination-related factors. Methods: Data were collected from routine occupational health surveillance conducted in 2023. Anti-HB titres were measured in 507 students, and information on age, sex, country of birth, age at vaccination, and time since the last dose was analysed. Results: Overall, 55.0% of students had antibody levels of at least 10 mIU/mL, indicating serological protection. Higher seroprotection rates were observed among students vaccinated in the first year of life compared to those vaccinated later. A significant decline in antibody titres was also associated with longer intervals since vaccination. Students born outside Europe tended to show lower levels of protection. Conclusions: These results emphasise the importance of screening future healthcare professionals and continuously monitoring antibody titres to help reduce HBV infections. Full article

Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article

Feline leishmaniasis (FeL), caused by Leishmania infantum, is increasingly reported in areas of endemic Mediterranean canine leishmaniasis (CanL), making it an emerging feline disease. This cross-sectional study investigated L. infantum seroprevalence and risk factors in 229 domestic cats from the Campania region of southern Italy, a CanL endemic area, between January 2023 and December 2024. Serum samples were tested for L. infantum antibodies (IFAT) and for FIV/FeLV. Seropositivity (IFAT titre ≥ 1:40) for FeL was detected in 12/229 (5.2%) of the cats tested. No statistically significant correlation was found between seropositivity for L. infantum and the variables considered. However, outdoor cats and FIV/FeLV-seropositive cats had higher prevalence rates: 10.6% and 7.4%, respectively. Of the 12 seropositive cats, 7 (58.3%) had an antibody titre of 1:40, 2 (16.6%) of 1:80 and 3 (25.0%) a titre of 1:160. Of the 12 cats positive for FeL, 2 (16.6%) were also positive for FIV. Our results confirm the exposure to L. infantum and the serological response in cats from southern Italy. The low prevalence could be due to owners using mosquito control products in the household that would also protect cats. Further investigation is essential to clarify risk factors and improve our understanding of the epidemiology of FeL in this endemic area. Full article

Background: Group A Streptococcus (GAS) is a major human pathogen associated with serious diseases. Evaluating immune responses against GAS vaccines—immunogenicity, quality, and efficacy—is complicated by interference from co-infections, like Staphylococcus aureus (S. aureus). We aimed to evaluate peptide-based GAS vaccines in mice for antisera efficacy against standard and mutant GAS strains and to assess immunological methods under co-infection conditions. Methods: Female C57BL/6 mice were infected with S. aureus and immunized with various M-protein-derived peptide antigens: J8, J8i, J8i-J8i, and the native p145 sequence. Two novel, conserved M-protein-derived antigens (NTD and CTD2) were also evaluated. Enzyme-linked immunosorbent assays (ELISAs) were used to assess immunogenicity and GAS-specific antibody responses. Peptide antigens were either conjugated to or physically mixed with the PADRE T-helper epitope and tested for enhanced antisera immunogenicity and opsonic efficacy. Result: ELISA against the immunizing peptides as coating antigens reflected the immunogenicity, while p145-based ELISA correlated with GAS-specific antibody titres without S. aureus interference for J8-based vaccines. Immunogenicity ranked J8 > J8i ≈ J8i-J8i > p145. NTD and CTD2 antisera demonstrated opsonic activity, indicating protective potential. PADRE–J8 conjugates significantly enhanced antibody magnitude and quality, producing strong opsonic bactericidal responses against both standard and p145-mutant GAS strains. PADRE–J8i was effective only against standard strains. This is the first report to suggest at least two B-cell epitopes within the J8i peptide. Conclusion: These findings support the diagnostic utility of p145, NTD, and CTD2 under co-infection settings, and the vaccine potential of J8, NTD, and CTD2, particularly when conjugated to a T helper for enhanced antigen presentation. Full article

Background: The COVID-19 pandemic highlighted the need for innovative vaccine platforms that elicit durable immunity. Self-amplifying RNA (saRNA) vaccines offer rapid production and dose-sparing advantages over traditional mRNA platforms. In Uganda’s first SARS-CoV-2 vaccine trial (NCT04934111), we assessed the safety and immunogenicity of a saRNA vaccine encoding the SARS-CoV-2 spike (S) glycoprotein in seronegative and seropositive adults. Methods: This non-randomised phase 1 trial (December 2021–April 2022) enrolled 42 healthy adults (18–45 years), including 12 seronegative and 30 seropositive for SARS-CoV-2. Participants received two 5 μg doses of saRNA vaccine, four weeks apart. Reactogenicity was assessed using diary cards for seven days post-vaccination, and adverse events were monitored throughout the 24-week study. Binding and neutralising antibody levels were quantified using ELISA and pseudovirus neutralisation assays. Findings: The vaccine was well tolerated, with only mild-to-moderate adverse events, including fatigue, headache, and chills. No serious vaccine-related events occurred. Among seronegative participants, 91.6% seroconverted after two doses (median S-IgG: 3695 ng/mL, p < 0.001). In the seropositive participants, S-IgG rose modestly from 7496 to 11,028 ng/mL after the second dose. Neutralising titres increased modestly across WT, BA.2, and A.23.1 variants, with no significant differences between groups. Conclusion: The saRNA SARS-CoV-2 vaccine was safe and immunogenic, inducing robust spike glycoprotein-specific antibody responses, particularly in seronegative participants. This trial demonstrates the potential of saRNA vaccines for broader use. Full article

Leishmaniasis by Leishmania infantum has a zoonotic transmission cycle involving an increasing number of mammalian hosts, forming a cooperative network. The sand fly feeding on livestock is evidenced, but clinical confirmation regarding their infection is limited. We aimed to evaluate Leishmania seroprevalence in livestock to assess its impact on leishmaniasis epidemiology in an endemic area located in the Mediterranean region. A cross-sectional serological study screened livestock exposure to L. infantum and risk factors in Southern Spain. A total of 864 serum samples of clinically healthy sheep, goats, cattle, and pigs were examined by an indirect fluorescence antibody test, using a 1/80 cut-off titre to minimize cross-reactions. Global seroprevalence was 10.8%: 21.6% cattle, 15.4% sheep, 7.3% goats, and 0.6% pigs. Statistically significant differences in positive detection were observed among species (p < 0.001) and natural regions (p < 0.001). High positive reactions in cattle, goats, and sheep suggest livestock exposure to Leishmania spp. and potential asymptomatic infection. Livestock presence in biotopes could promote a dilution effect, reducing human leishmaniasis incidence. Further investigation is needed to confirm livestock roles in leishmaniasis maintenance and transmission. Full article

Periodontitis and type 2 diabetes mellitus are interconnected in a bidirectional relationship, yet the underlying mechanisms remain poorly understood. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been implicated in both conditions. This study investigates the association between antibody responses to P. gingivalis and the coexistence of periodontitis and diabetes, aiming to explore its potential as a biomarker for early screening. The developed enzyme linked immunosorbent assay (ELISA) was used to analyse in a pilot study the serum of subjects with periodontitis (n = 26), subjects with periodontitis and type 2 diabetes mellitus (n = 15), and healthy individuals (n = 13) for immunoglobulin (Ig)G- and IgM-antibody titres against FimA. A statistically significant difference (p < 0.001) between the IgG titres of the three study groups was observed. Patients with periodontitis and type 2 diabetes mellitus showed the highest IgG titres and thus the highest level of IgG antibodies, followed by periodontitis patients and finally the orally healthy subjects. This study demonstrated the establishment of a reliable and reproducible ELISA for the detection of antibodies against FimA from P. gingivalis W83. In addition, the outcomes of this study can be used to develop a screening assay that can indicate existing periodontitis and type 2 diabetes mellitus based on IgG antibody titres against FimA from P. gingivalis. Full article

Objective: To assess changes in disease activity in Multiple Sclerosis (MS) patients on various disease-modifying-drugs, as well as immunogenicity, safety and clinical tolerability following combined tetanus- and diphtheria-vaccination. Methods: We conducted a prospective, multicentre, non-randomised real-world observational study at specialised outpatient MS care centres in Germany. We enrolled multiple sclerosis patients receiving a combined tetanus- and diphtheria-vaccination who had a stable MS-treatment regimen for at least six months and had an indication for this vaccination. Serum samples were obtained before and four weeks after vaccination for specific antibody response. Antibody concentrations against vaccine antigens were measured in duplicate via ELISA. Subjects were followed for one year after immunisation. MS disease activity (EDSS and relapse rates) was evaluated at follow-up visits. Local and systemic adverse events were registered four weeks after vaccination. Results: In total, 72 MS patients received tetanus and diphtheria vaccination. The annualised relapse rates in the year after vaccination were comparable to the year before vaccination (0.39 vs. 0.37). During the study period, the EDSS score did not change significantly. The score was 2.0 and 2.2 in the two years prior to vaccination and 2.5 in the year following vaccination. No subjects experienced severe adverse events. However, 14 (19.4%) had local adverse events, and 10 (13.9%) had systemic reactions. Following vaccination, all subjects had protective antibody titres against tetanus- and diphtheria-toxoid. Geometric mean antibody titres of tetanus toxoid antibodies increased from 0.64 IU/mL to 2.23 IU/mL (p < 0.0001) and of diphtheria toxoid antibodies from 0.1 IU/mL to 0.45 IU/mL (p < 0.0001). Conclusions: Tetanus- and diphtheria vaccination proved to be safe and effective in MS patients in a real-world situation. Full article

Objectives: This study investigated whether serum soluble CD200 (sCD200) and soluble receptor for CD200 (sCD200R) concentrations and serum sCD200/sCD200R ratios at diagnosis could predict cross-sectional activity in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We included 70 patients with AAV in this pilot study, retrospectively reviewed their medical records, and collected clinical data at the time of AAV diagnosis. We also measured sCD200 and sCD200R in stored blood samples collected at diagnosis. In medical records, AAV activity at diagnosis had been assessed according to the Birmingham Vasculitis Activity Score (BVAS). The prediction potential of serum sCD200 and sCD200R concentrations and serum sCD200/sCD200R ratios for BVAS was evaluated using Pearson correlation analysis. Results: Among the 70 patients, the median age was 63.5 years, with 29 males and 41 females. Among the three CD200-related variables at diagnosis, serum sCD200/sCD200R ratios at diagnosis were significantly correlated with cross-sectional BVAS; however, serum sCD200 and sCD200R concentrations were not correlated with it. These results may indicate that serum sCD200/sCD200R ratios may better help predict cross-sectional AAV activity by increasing the range of opposing changes in the two variables. On the other hand, both serum sCD200 concentrations and serum sCD200/sCD200R ratios showed significant correlations with cross-sectional myeloperoxidase-ANCA titre, five-factor score, and serum creatinine levels at diagnosis. Conclusions: In this study, we demonstrated that serum sCD200/sCD200R ratios at diagnosis can be a useful and convenient biomarker to predict cross-sectional AAV activity calculated according to BVAS. Full article

Measles remains an important cause of morbidity and mortality worldwide. Most HIV-infected adults are immune against measles, so titres of measles antibodies should be determined prior to vaccination. A measles vaccine can be administered to HIV-positive patients who do not have protective antibody levels and who have a CD4 lymphocyte count ≥ 200 cells/mm³. We describe the case of an HIV-infected patient, diagnosed with complicated measles at our Infectious Diseases Hospital in April 2024. Full article

Background: The global SARS-CoV-2 pandemic revealed stark variability in clinical outcomes across populations, underscoring the need for region-tailored vaccination strategies. To inform standardised global immunisation efforts, this study compared longitudinal binding antibody responses and neutralisation capacities in mild COVID-19 cases from Uganda and the United Kingdom (UK). Methods: IgG responses to spike (S) and nucleocapsid (N) proteins, along with IgM responses to S and receptor-binding domain (RBD) proteins, were assessed in 29 Ugandan and 14 UK participants over 84 and 82 days, respectively. Antibody levels were quantified using a validated enzyme-linked immunosorbent assay (ELISA), alongside pseudovirus neutralisation assays targeting the D614G variant. Results: Ugandan participants exhibited higher early IgG and IgM levels, particularly against spike and RBD, with a rapid onset of responses that waned quickly. UK participants showed a slower but sustained increase in IgG and IgM levels. Neutralisation titres revealed elevated responses in 16.4% of Ugandan participants (>2000) compared to 4.5% of UK participants, suggesting a greater sensitivity to viral neutralisation. Conversely, 31.8% of UK participants exhibited low titres (<25) compared to 14.8% of Ugandan participants, indicating differences in resistance mechanisms. Neutralisation correlated strongly with spike and receptor-binding domain IgG in the UK cohort but showed weaker correlations in Ugandan participants. Conclusions: These findings highlight distinct population-level immune responses, suggesting that geographic factors shaped the quality and durability of SARS-CoV-2 immunity. Tailored vaccination strategies are essential to optimise immunity across diverse populations and improve global epidemic preparedness. Full article

We previously reported on HIV vaccines that elicited autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. In the current study, we sought to establish a proof of concept that HIV vaccines using identical designs elicit Tier 2 nAbs in arhesus macaque (RM) model. DNA and MVA vaccines expressing SIV Gag and HIV-1 Env antigens were constructed, and in vitro expression was confirmed. A soluble envelope protein (gp140 Env) was expressed from a stable HEK293 cell line and purified using lectin affinity and size exclusion chromatography. The expression and secretion of SIV Gag and HIV-1 Env by the DNA and MVA vaccines was verified in vitro. Five RMs were inoculated with two DNA, followed by two MVA, and finally with two gp140 Env vaccines at weeks 0, 4, 8, 12, 20 and 28. Vaccine-induced T cell immunity was measured by IFN-γ ELISpot while nAbs were evaluated against MW965 (Tier 1A), 6644 (Tier 1B), autologous ZM109.5A and a closely-related ZM109.B4 (Tier 2) pseudovirions. Vaccinated RMs were challenged intrarectally with simian-human immunodeficiency virus (SHIV), four weeks after the final vaccination, as was an unvaccinated control group (n = 4). Following vaccination, all the animals developed moderate IFN-γ ELISpot responses after the DNA vaccinations which were boosted by the MVA vaccine. After the gp140 Env boost, all animals developed nAbs with peak median titres at 762 (MW965) and 263 (ZM109.5A). The vaccinated animals became infected after a similar number of challenges to the unvaccinated controls, and the resultant number of viral copies in the blood and the lymphoid tissues were similar. However, the duration of detectable viraemia in the vaccinated animals (median: 2 weeks) was shorter than the controls (median: 8.5 weeks). These data show that the vaccines elicited robust cellular and functional humoral immune responses that resulted in a quicker control of viraemia. Full article

Background and Objectives: Autoimmune thyroid diseases are more prevalent in patients diagnosed with Sjögren disease (SD) than in the general population. SD and autoimmune thyroid diseases are two distinct yet interrelated autoimmune disorders. The objective of this study was to determine the frequency of autoimmune thyroiditis (AT), autoantibody relationships, and clinical features in patients with SD. Materials and Methods: The study included 525 patients. A retrospective evaluation was conducted on the demographic data, biochemical and serological tests, and pathological data of the patients. An anti-nuclear antibody (ANA) test was performed using the indirect immunofluorescence (IIF) method using HEp-2 (HEp-2000) cells as substrate. The Schirmer test and minor salivary gland biopsy were conducted on all patients. Results: AT was detected in 167 (31.8%) of 525 patients who participated in the study. The anti-nuclear antibody (ANA) test and anti-SS-A positivity rate were higher in the AT group (p value < 0.001 and 0.002 respectively). We found that the likelihood of developing AT increased as ANA titres increased. ANA positivity titres were found to be significant at 2+, 3+, and 4+ values (odd ratios 2.41, 3.40, and 4.21, respectively). Additionally, histological examination of salivary gland biopsies revealed a significantly higher prevalence of diffuse lymphocytic infiltration in the AT group. Conclusions: AT was present in 31% of patients with SD. The presence of ANA positivity, anti-SS-A positivity, and diffuse lymphocytic infiltration appears to exert an influence on the association between these two diseases. Full article