Search Results (551)

Background: Children with inflammatory bowel disease (IBD) are at heightened risk for vaccine-preventable infections because of underlying immune dysregulation and long-term immunosuppressive therapy. Despite published guidelines affirming vaccine safety, real-world coverage remains suboptimal. It is a pilot, single-country survey designed to explore baseline knowledge and practices regarding vaccination in paediatric IBD within a specific local healthcare context. Objective: The objective of this study is to evaluate the knowledge, attitudes, and practices of paediatric gastroenterologists (PGs) regarding the immunisation of children with IBD. Methods: We conducted an exploratory pilot, cross-sectional survey of paediatric gastroenterologists in Russia, focusing on immunisation knowledge and practical barriers in routine care. A cross-sectional, anonymous online survey was distributed to PGs nationwide between January 2022 and April 2022. The online questionnaire explored demographic characteristics, awareness of international recommendations, perceptions of vaccine safety at various disease and treatment stages, and routine vaccination practices. Responses were analysed with non-parametric statistics (α = 0.05). In a parallel prospective cohort, the vaccination certificates of 98 paediatric IBD patients (January 2022–April 2023) were audited to quantify real-world coverage. Results: Fifty-one PGs completed the survey. Forty-one per cent agreed that vaccines do not provoke IBD flares, while 17.6% considered live vaccines acceptable during immunosuppressive remission. Nearly one-third (32%) did not personally oversee immunisation, and 18% occasionally discouraged vaccination during therapy. Only 35.3% deemed baseline serology essential before starting immunosuppression; 46.5% supported antibody checks immediately prior to vaccination. The certificate audit revealed a full schedule completion rate of 66.3% for measles–mumps–rubella and 74.2% for hepatitis B, contrasting with parental reports of 82.3% complete coverage. Conclusions: Knowledge gaps, limited guideline awareness, and parental concerns contribute to suboptimal vaccination of paediatric IBD patients. Targeted educational initiatives, clearer shared-care pathways, and routine certificate audits are needed to close the coverage gap and reduce infection-related morbidity. Findings are hypothesis-generating and reflect local practice; as a pilot study, results should be interpreted with caution and may not generalise beyond similar settings. Full article

Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV. Existing treatment options, including pegylated interferon-α and hepatocyte entry inhibitors, offer limited efficacy. Emerging therapeutic strategies are focused on targeting various steps of the HDV life cycle or enhancing the host immune response to promote viral elimination. A defective antiviral immune response is increasingly recognized as a culprit for HDV persistence; however, the precise immunological mechanism associated with disease progression and pathogenesis has not been well defined. This review provides an update on the current understanding of host immune response in CHD, highlighting its role in both disease pathogenesis and viral clearance. A deeper understanding of these immune correlates may lead the way to novel treatment strategies, including immunotherapies targeting host immune response that can be used in combination with other antiviral therapies to achieve more effective and durable treatment outcomes. Full article

Background: Despite virological suppression through antiretroviral therapy (ART), people living with HIV (PLHIV) may exhibit inadequate immune responses to vaccination, placing them at continued risk for preventable infectious diseases. Evidence regarding the durability of vaccine-induced immunity in PLHIV with vertically acquired infection remains limited. Methods: We conducted a cross-sectional observational study to evaluate humoral immunity to routine childhood vaccines in a cohort of PLHIV with perinatally acquired infection. Antibody titers against diphtheria, tetanus, measles, mumps, rubella, varicella, and hepatitis B (HBV) were retrospectively assessed via serological testing and review of medical records. Seroprotection rates were analyzed at predefined intervals following the completion of the primary immunization schedule. Multivariate analysis was used to explore potential predictors of long-term immune response. Results: A total of 85 individuals were included. Two years after completing the primary vaccination series, seroprotection rates were as follows: diphtheria 71%, tetanus 79%, measles 79%, mumps 67%, rubella 87%, and varicella 54%. Five years post-vaccination, 50–70% of participants maintained protective antibody levels, declining further to 50–58% after ten years. By twenty years, protective immunity dropped below 30% for all antigens except rubella (47%). HBV vaccine responses were notably poor, with only 60%, 37%, 24%, and 7.5% retaining protective anti-HBs titers at 2, 5, 10, and 20 years post-immunization, respectively. Time elapsed since vaccination was the sole significant predictor of seroprotection across all vaccines. Conclusions: In this cohort of vertically infected PLHIV, vaccine-induced immunity was suboptimal and declined markedly over time compared to the general population. These findings highlight the need for tailored immunization strategies, including timely boosters and regular serological monitoring, to maintain long-term protection in this high-risk group. Full article

Background/Objectives: Identifying dietary factors influencing liver cancer is crucial for developing preventive measures. While tea polyphenols have demonstrated cancer-preventive activities in animal models, the evidence in humans is not definitive. This study aims to explore the association between tea consumption and liver cancer, as well as the interaction between tea drinking and other risk factors, in China, a country with a high incidence of liver cancer and substantial tea consumption. Methods: A population-based case–control study was conducted in Jiangsu Province from 2003 to 2010. Socio-demographic data, history of tea consumption, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were evaluated. Unconditional logistic regression was used to examine the associations between tea consumption and the odds of liver cancer. Potential interactions between tea consumption and other major liver cancer risk factors were assessed. Results: A total of 2011 incident liver cancer cases and 7933 controls were included in the analysis. Regular tea drinking showed an inverse association with the risk of liver cancer compared with those who never drank tea (OR: 0.79; 95% CI: 0.63–0.99). Current tea drinking showed an inverse association with liver cancer (OR: 0.51; 95% CI: 0.39–0.66), while former tea drinking showed a positive association (OR: 3.56; 95% CI: 2.42–5.23). Current tea consumption was inversely associated with liver cancer incidence among both hepatitis B surface antigen (HBsAg) positive (OR: 0.45; 95% CI: 0.28–0.73) and HBsAg negative participants (OR: 0.51, 95% CI: 0.36–0.73), among both never and ever tobacco smokers, ever alcohol drinkers (OR: 0.46; 95% CI: 0.33–0.63), and among those without family history of liver cancer. Multiplicative and additive interactions were observed between tea drinking and HBsAg, alcohol consumption, and history of raw water drinking. Conclusions: Tea consumption is inversely associated with the development of primary liver cancer, with potential interactions involving HBV infection, alcohol consumption, and raw (unsafe) water drinking. Increasing tea consumption—particularly among high-risk populations such as individuals who consume alcohol—may serve as an additional preventive measure for liver cancer. This should be considered alongside established strategies, including HBV vaccination, alcohol cessation, and avoidance of drinking raw water, to help reduce liver cancer risk. Full article

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

Anthrax remains a formidable bioterrorism threat for which new, optimized and thermostable vaccines are needed. We previously demonstrated that five immunizations of rabbits with a multiple-antigenic-peptide (MAP) vaccine in either Freund’s adjuvant or human-use adjuvants can elicit antibody (Ab) against the loop-neutralizing determinant (LND), a cryptic neutralizing epitope in the 2β2-2β3 loop of protective antigen from Bacillus anthracis (B. anthracis), which mediates complete protection of rabbits from inhalation spore challenge with the B. anthracis Ames strain. To develop a more immunogenic vaccine, we molecularly constructed a virus-like particle (VLP) vaccine, comprising the Woodchuck hepatitis core antigen capsid (WHcAg) displaying 240 copies of the LND epitope on each nanoparticle. Initial studies showed that the LND-VLP was immunogenic in rabbits following two immunizations, and passive transfer of the rabbit sera into A/J mice conferred complete protection from aerosol challenge with B. anthracis. Further optimization of the vaccine revealed that the lyophilized LND-VLP vaccine was capable of eliciting highly protective levels of neutralizing antibody with two immunizations, and in some rabbits, a single immunization, using human-use adjuvants. A lyophilized LND-VLP nanoparticle vaccine may be an effective stand-alone vaccine or may complement PA-based vaccines as a future pre- or post-exposure vaccine for anthrax. Full article

In Nigeria, hepatitis B virus (HBV) infection remains a significant public health issue. The emergence of immune escape mutants (IEMs), basal core promoters, and precore (BCP/PC) mutants among asymptomatic individuals has enabled the continuous evolution of the virus in the country. In this study, we used Sanger sequencing of the S gene and the BCP/PC region to investigate the genetic diversity, phylogenetic relationships, and mutational profiles of HBV strains detected in two regions in Nigeria. A total of 178 HBsAg-positive samples confirmed by ELISA underwent viral DNA extraction and PCR amplification of the surface and BCP/PC genes, and 76 and 60 sequences were found to be exploitable for S and BCP/PC genes, respectively, which were used for HBV genotyping and mutational analysis. We detected various mutations in the major hydrophilic loop (target of neutralizing antibodies), including vaccine escape mutants (VEMs) (L127P/R, S140T/L, and G145A), HBV immunoglobulin resistance mutants (T131N, S143T, and W156R), and mutations previously reported in patients with reactivated infections (T115N, G159A/R, and F161Y). We also identified a high proportion of C1741T in 34/42 (81%) along with A1762T or G1764A mutation in 14/42 (33%) and 18/42 (43%) as the dominant variants in the BCP region. The predominant classical PC G1896A and G1899A variants were identified in 26/42 (62%) and 17/42 (40%) participants in this study. Two HBV genotypes were identified (A and E). However, HBV genotype E was the most frequently identified genotype, and is still the dominant strain circulating in Nigeria. We report the circulation of HBV IEMs and the preponderance of BCP and classical PC variants among asymptomatic carriers. Our findings suggest that the spread of these HBV mutant variants among asymptomatic carriers may have an impact on the effectiveness of diagnostic immunoassays and the success of HBsAg-based vaccinations. This highlights the need for robust surveillance. Full article

Background/Objectives: Glucan particles (GPs), derived from Saccharomyces cerevisiae yeast, possess unique biomedical properties. Nevertheless, it is imperative that a comprehensive risk assessment is conducted during pre-clinical development. GPs are primarily constituted of a naturally occurring polymer known as β-glucan. This study characterized GPs, focusing on physicochemical attributes, biocompatibility, and immunomodulatory potential. Methods: GPs were characterized for size, morphology, surface charge, and protein encapsulation efficiency using dynamic light scattering (DLS), electron microscopy, and encapsulation assays. Biocompatibility was assessed through cytotoxicity assays (MTT), hemolysis tests, and measurement of reactive oxygen (ROS) and nitric oxide (NO) production in immune cells. Immunomodulatory potential was evaluated by cytokine and chemokine secretion analysis in peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs) and through in vivo immunization studies in a murine model, focusing on cellular immune responses. Results: GPs demonstrated stable physicochemical properties and efficient protein encapsulation, highlighting their suitability as vaccine delivery systems. They exhibited biocompatibility by not inducing cytotoxicity, hemolysis, or excessive ROS and NO production. In PBMCs, GPs stimulated cytokine secretion, suggesting their adjuvant potential. GPs were efficiently internalized by monocytes and led to specific chemokine secretion in stimulated moDCs. In a murine model, GPs induced distinctive cellular immune responses, including TNF-α and IFN-γ production and effector memory T cell activation. Conclusions: These findings emphasize GPs’ biocompatibility and immunomodulatory effects, highlighting their potential in immunotherapy and vaccine development, particularly for targeting infectious agents like hepatitis B virus. Full article

Background: Assessment of efficacy in HIV prevention trials remains a challenge in the era of widespread use of active controls. We investigated use of counterfactual groups to assess treatment efficacy. Methods: We used data from placebo arms of two previous HIV prevention efficacy trials (Pro2000 vaginal microbicide trial, 2005–2009: ISRCTN64716212 and dapivirine vaginal ring trial, 2013–2016: NCT01539226) and four observational cohorts (two in each of the periods; (a) during the conduct of a simulated HIV vaccine efficacy trial (SiVET), 2012–2017, and (b) prior to SiVET (2005–2011)) and compared HIV prevention efficacy trial targeted outcomes with SiVETs. SiVET participants were administered a licensed hepatitis B vaccine at 0, 1 and 6 months mimicking an HIV vaccine efficacy trial schedule. Participants were tested for HIV quarterly for one year. The probability of the SiVET assignment conditioned on the measured participants’ baseline characteristics were estimated using propensity scores (PS) and matched between SiVET and placebo arm of trials. Similar calculations were repeated for observational cohorts in the pre- and during SiVET periods. We compared HIV incidence rate ratio (IRR) between SiVET and the trials or observational data before and after PS matching. Results: This analysis involved data from 3387 participants; observational cohorts before SiVET 1495 (44.2%), placebo arms of previous trials 367 (10.8%), observational cohorts during SiVET conduct 953 (28.1%) and SiVETs 572 (16.9%). Before propensity score matching (PSM), there were significant imbalances in participants’ baseline characteristics between SiVET, and all the other studies and HIV incidence was lower in SiVET. After PSM, the participants’ characteristics were comparable. The HIV incidence in SiVET was similar to that in the previous trial, IRR = 1.01 95% CI: 0.16–4.70), p = 0.968, and observational data during SiVET, IRR = 0.74, 95% CI 0.34–1.54), p = 0.195, but much lower compared to the observational data pre-SiVET, IRR = 0.48, 95% CI: 0.20–1.04), p = 0.023. Conclusions: PSM can be used to create counterfactual groups from other data sources. The best counterfactual group for assessing treatment effect is provided by data collected in the placebo arm of previous trials followed by that from observational data collected concurrently to the current trial (SiVET). Even with PSM, observational data collected prior to the current trial may overestimate treatment effect. Full article

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely eradicate covalently closed circular DNA (cccDNA) reservoirs. Moreover, vaccination does not offer therapeutic benefit to already infected individuals or non-responders. Consequently, chronic infection is maintained by the persistence of cccDNA in infected hepatocytes. For this reason, novel therapeutic strategies that permanently inactivate cccDNA are a priority. Obligate heterodimeric transcription activator-like effector nucleases (TALENs) provide the precise gene-editing needed to disable cccDNA. To develop this strategy using a therapeutically relevant approach, TALEN-encoding mRNA targeting viral core and surface genes was synthesized using in vitro transcription with co-transcriptional capping. TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in a liver-derived mammalian cell culture model of infection. In a stringent HBV transgenic murine model, a single dose of hepatotropic lipid nanoparticle-encapsulated TALEN mRNA lowered HBsAg by 63% and reduced viral particle equivalents by more than 99%, without evidence of toxicity. A surveyor assay demonstrated mean in vivo HBV DNA mutation rates of approximately 16% and 15% for Core and Surface TALENs, respectively. This study presents the first evidence of the therapeutic potential of TALEN-encoding mRNA to inactivate HBV replication permanently. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs. Full article

Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980. Additionally, there has been a remarkable 99.9% reduction in wild poliovirus cases since 1988, decreasing from more than 350,000 cases that year to just 30 cases in 2022. Objectives: The objective of this review was to assess the effects of various interventions designed to increase vaccination uptake among adults. Search Methods: A thorough search was conducted in the CENTRAL, Embase Ovid, Medline Ovid, PubMed, Web of Science, and Global Index Medicus databases for primary studies. This search was conducted in August 2021 and updated in November 2024. Selection Criteria: Randomized trials were eligible for inclusion in this review, regardless of publication status or language. Data Analysis: Two authors independently screened the search outputs to select potentially eligible studies. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for each randomized controlled trial (RCT). A meta-analysis was conducted using a random-effects model, and the quality of the evidence was assessed using the GRADE approach. Main Results: A total of 35 randomized controlled trials met the inclusion criteria and were included in this review, with the majority conducted in the United States. The interventions targeted adults aged 18 and older who were eligible for vaccination, involving a total of 403,709 participants. The overall pooled results for interventions aimed at increasing influenza vaccination showed a risk ratio of 1.41 (95% CI: 1.15, 1.73). Most studies focused on influenza vaccination (18 studies), while the remaining studies examined various other vaccines, including those for hepatitis A, COVID-19, hepatitis B, pneumococcal disease, tetanus, diphtheria, pertussis (Tdap), herpes zoster, and human papillomavirus (HPV). The results indicate that letter reminders were slightly effective in increasing influenza vaccination uptake compared to the control group (RR: 1.75, 95% CI: 0.97, 1.16; 6 studies; 161,495 participants; low-certainty evidence). Additionally, participants who received education interventions showed increased levels of influenza vaccination uptake compared to those in the control group (RR: 1.88, 95% CI: 0.61, 5.76; 3 studies; 1318 participants; low-certainty evidence). Furthermore, tracking and outreach interventions also led to an increase in influenza vaccination uptake (RR: 1.87, 95% CI: 0.78, 4.46; 2 studies; 33,752 participants; low-certainty evidence). Conclusions: Letter reminders and educational interventions targeted at recipients are effective in increasing vaccination uptake compared to control groups. Full article

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. 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