Search Results (18)

Background: Hepatitis B virus (HBV) is a major cause of morbidity and mortality globally, and chronic infections are associated with cirrhosis and hepatocellular carcinoma. Issues with conventional treatments and vaccines mean there is a need for new therapeutic vaccines, which must elicit a strong and sustainable immune response. Here, we evaluated the immunogenicity of dual-antigen vaccines containing hybrid surface (hy-LHBs) and core (HBc) antigens, combined with a carboxyl-vinyl polymer (CVP) as a mucoadhesive excipient, following intranasal administration in mice. Methods: Mice were intranasally administered a mixed vaccine (10 µg of hy-LHBs and 2.5 or 10 µg of HBc) with or without a CVP excipient, and they were assessed for their immune response (levels of IgGs or IgA antibodies in an ELISA, IFN-γ level in splenocytes in an ELISpot assay, and cytokine/chemokine levels in a BioPlex assay). A protein stability assay was also conducted for vaccine formulations with and without excipients. Results: Significantly enhanced IgG production was noted targeting hy-LHBs and (less markedly) HBc at 10 µg/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 µg HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1α (#00, #00-07, 0B), and MCP-1 (#00-07, 0B) in mice that received treatment compared to those of untreated mice. The endpoint titers of IgG1 and IgG2a were measured, which were higher with CVP excipients than without. From the IgG2a/IgG1 ratio, a higher IgG1 response was induced by CVPs to hy-LHBs and a higher IgG2a response was induced to HBc. Th2-dominant phenotype to hy-LHBs was induced with CVP#00 in an ELISpot assay. The highest anti-hy-LHBs antibody titer was noted with the conventional CVP#00 excipient. Consistent with these results, a higher amount of neutralizing antibodies of HBV was induced with CVP#00 treatment and followed by #00-03 and #14-00. Conclusions: We consider that the addition of CVP excipients to vaccine formulation enhances immunogenicity and HBV antigen stability for intranasal vaccines. This effect was seen for both humoral and cell-mediated immune responses, indicating the potential of CVPs as excipients in intranasal HBV vaccines. Full article

Hymenoptera venom allergy (HVA) is an IgE-mediated hypersensitivity reaction caused by Hymenoptera species stings (honeybee, vespid, or ant). The only effective treatment is Hymenoptera venom immunotherapy (VIT). Our study aimed to evaluate whether humoral and cellular biomarkers measured before, during, and after honeybee VIT are associated with the success of VIT, which was assessed by the response to a sting challenge one year after finishing VIT. In this prospective study, blood biomarkers of 25 patients undergoing honeybee VIT at the referral center in Slovenia were evaluated. A controlled honeybee sting challenge confirmed successful VIT in 20 of 25 (80%) patients. Honeybee venom (HBV) recombinant allergen profiles, evaluated before the treatment, were comparable between responders and non-responders. Longitudinal follow-up, up to 1 year after finishing VIT, showed that the immune responses do not differ significantly between patients with successful VIT and treatment failure. Those responses were characterized by decreased sIgE, tIgE, and BST, whereas sIgG4 levels increased. The basophil sensitivity also significantly decreases after VIT in both groups of patients. The analyzed biomarker which correlated considerably with treatment failure was higher basophil sensitivity to allergen stimulation before VIT. Similarly, systemic adverse events (SAEs) during the build-up phase of VIT correlated with treatment failure. Our study demonstrated similar sensitization profiles, and humoral and basophil immune responses to immunotherapy, in two different well-characterized groups of patients, one with successful VIT and the other with treatment failure. Notably, only high basophil sensitivity measured before VIT and SAEs during VIT were significantly associated with VIT failure, and both have the potential to be predictors of VIT failure. Full article

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously introduced clinical model of host–virus interaction (i.e., infectious process in immunodeficiency) for analysis of B cells and the specific IgG role (an observational study of a CVID patient who received intravenous immunoglobulin (IVIG). Suddenly, the patient deteriorated and a positive results of for HBs and HBV-DNA (369 × 10⁶ copies) were detected. Despite lamivudine therapy and IVIG escalation (from 0.3 to 0.4 g/kg), CT showed an 11 cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs were positive in time-lapse analysis (range 111–220 IU/mL). Replacement therapy intensification was complicated by an immune complex disease with renal failure. Fulminant HCC in CVID and the development of a tumor as the first sign is of interest. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HB substitution has not been proven to be effective, oncoprotective, nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, and patient selection more precise with the exclusion of HBV-positive donors. Our clinical model showed an HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g., chronic hepatitis). The lack of cell cooperation as well as B cell deficiency observed in CVID play a crucial role in high HBV replication, especially in carcinogenesis. Full article

Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut–liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies. Full article

The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as combined vaccine candidates in rhesus monkeys. The HEV and HBV components consisted of 450 bps, neutralizing the epitope/s (NE) region, and 685 bps small (S) envelope gene-corresponding proteins, respectively. Three groups (n = 2 monkeys/group) were intramuscularly immunized with a total of three doses of NE Protein (Lipo-NE-P), NE DNA + Protein (Lipo-NE-DP), and each of NE and S DNA + Protein (Lipo-NES-DP), respectively, given one month apart. All immunized monkeys were challenged with 10,000 fifty percent monkey infectious dose of homologous HEV strain. Post-immunization anti-HEV antibody levels in monkeys were 59.4 and 148.4 IU/mL (Lipo-NE-P), 177.0 and 240.8 IU/mL (Lipo-NE-DP), and 240.7 and 164.9 IU/mL (Lipo-NES-DP). Anti-HBV antibody levels in Lipo-NES-DP immunized monkeys were 58,786 and 6213 mIU/mL. None of the challenged monkeys showed viremia and elevation in serum alanine amino transferase levels. Monkeys immunized with Lipo-NE-DP and Lipo-NES-DP exhibited a sterilizing immunity, indicating complete protection, whereas monkeys immunized with Lipo-NE-P showed limited viral replication. In conclusion, the liposome-complexed DNA-corresponding proteins of HEV and HBV induced protective humoral immune responses to both components in monkeys and are worth exploring further. Full article

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN–RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma. Full article

The immune system in humans is regulated by the circadian rhythm. Published studies have reported that the time of vaccination is associated with the immune response to vaccine for some pathogens. Our study aimed to evaluate the association between time of dose administration of challenge HBV vaccine and seroconversion for anti-HBs in medical students vaccinated at birth who were found to be unprotected at pre-training screening. Humoral protection for HBV was assessed in 885 medical students vaccinated during childhood. In total, 359 (41.0%) of them showed anti-HBs titer < 10 UI/mL and received a challenge dose of HBV vaccine followed by post-vaccination screening 30–60 days later. The challenge dose elicited a protective immune response (anti-HBs IgG titer > 10 UI/mL) in 295 (83.8%) individuals. Seroconversion was significantly associated with female gender and time of vaccination after controlling for age group and nationality at logistic regression analysis. Students who received the booster dose in the morning had a higher response rate than those who received the vaccine in the afternoon (OR 1.93; 95% C.I. 1.047–3.56: p < 0.05). This finding suggests that morning administration of the HBV booster may result in a better immune response in susceptible individuals. Full article

Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. Although the virus encodes just two forms of its single antigen, it enhances the progression of liver disease to cirrhosis in CHB patients and increases the incidence of hepatocellular carcinoma. HDV pathogenesis so far has been attributed to virus-induced humoral and cellular immune responses, while other factors have been neglected. Here, we evaluated the impact of the virus on the redox status of hepatocytes, as oxidative stress is believed to contribute to the pathogenesis of various viruses, including HBV and hepatitis C virus (HCV). We show that the overexpression of large HDV antigen (L-HDAg) or autonomous replication of the viral genome in cells leads to increased production of reactive oxygen species (ROS). It also leads to the upregulated expression of NADPH oxidases 1 and 4, cytochrome P450 2E1, and ER oxidoreductin 1α, which have previously been shown to mediate oxidative stress induced by HCV. Both HDV antigens also activated the Nrf2/ARE pathway, which controls the expression of a spectrum of antioxidant enzymes. Finally, HDV and its large antigen also induced endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR). In conclusion, HDV may enhance oxidative and ER stress induced by HBV, thus aggravating HBV-associated pathologies, including inflammation, liver fibrosis, and the development of cirrhosis and hepatocellular carcinoma. Full article

Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor’s immune environment, it is essential to understand the immune environment of hepatocellular carcinoma to select ICI therapeutic indications and develop biomarkers. A network of diverse cellular and humoral factors establishes cancer immunity. By analyzing individual cases and classifying them from the viewpoint of tumor immunity, attempts have been made to select the optimal therapeutic drug for immunotherapy, including ICIs. ICI treatment is discussed from the viewpoints of immune subclass of HCC, Wnt/β-catenin mutation, immunotherapy in NASH-related HCC, the mechanism of HPD onset, and HBV reactivation. Full article

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018–2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018–2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination. Full article

Background: Understanding immune responses after HBV vaccination is important to prevent HBV infection in PLWH and to achieve successful treatment. Methods: Thirty-two PLWHs with CD4⁺ cell count > 350 cells/µL and HIV RNA < 200 copies/mL were vaccinated with 20 µg of HBV vaccine at weeks 0, 4, and 24 in this prospective study. We measured total HIV DNA levels, HBsAb titers and HBsAg-specific T-cell responses during follow-up time. Results: All patients achieved protective HBsAb titer after immunization. The magnitude of the IFN-r and TNF-a response to HBsAg was 22.0 (IQR: 6.5–65.0) and 106.50 (IQR: 58.5–203.0) spot-forming cells (SFC)/10⁵ PBMC, respectively at week 0. The level of IFN-r secreted at weeks 12 and weeks 36 to 48 was comparable with that at week 0. However, IFN-r response was higher at weeks 12 than that at weeks 36 to 48 (p = 0.02). The level of TNF-a secreted at weeks 12 was higher than that at week 0 (p < 0.001). Total HIV DNA levels were 2.76 (IQR: 2.47–3.07), 2.77 (IQR: 2.50–3.09), 2.77 (IQR: 2.41–2.89) log₁₀ copies/10⁶ PBMCs at weeks 0, 12, 36 to 48, respectively. No correlation was observed between IFN-r and TNF-a levels and HBsAb titer as well as total HIV DNA levels after immunization. Conclusion: Humoral immunity was satisfactory, but cellular immunity and decline in HIV reservoir were not optimal after HBV vaccine immunization in these patients. Full article

Hepatitis B virus represents an important global health problem. In highly developed countries, mass vaccination campaigns of newborns in recent decades have drastically reduced the proportion of carriers. However, workers exposed to blood and body fluids, including healthcare students, can be at risk of exposure. In order to assess the proportion of susceptible individuals in the specific population of healthcare students in highly developed countries, a systematic review and meta-analysis was performed to summarize the evidence on the persistence of humoral immune protection induced by the primary cycle of hepatitis B vaccination, as well as the proportion of true non-responders. Forty-six studies were included in the final analysis (52,749 participants). Overall, the seroprotection prevalence at the pre-exposure assessment was equal to 73.8% (95% CI 69.1–78.0); the prevalence of anamnestic response following the administration of a challenge dose was 90.9% (95% CI 87.7–93.3), demonstrating a high proportion of persistence of vaccination-induced immunity. Among those without evidence of anamnestic response, 5.0% (95% CI 2.1–11.5) were non-responders following the completion of a secondary immunization cycle. These findings demonstrate that the majority of healthcare students vaccinated with the complete HBV primary cycle maintain an effective humoral immunity against this pathogen for over two decades. Full article

Maintenance hemodialysis (MHD) patients have impaired immunological responses to pathogens and vaccines. In this study, we compared the humoral response to HBV and COVID-19 vaccines in a cohort of MHD patients. Demographic and clinical characteristics of vaccine responders and non-responders were also compared, and the association between the humoral responses to both vaccines was evaluated. The cohort included 94 MHD patients who were vaccinated at least once for HBV and twice for COVID-19. Among the 94 patients, 28 (29.8%) did not develop protective titers to HBV. Hypertension, coronary heart disease, and heart failure were more common in non-responders. Among MHD patients, 85% had positive IgG anti-spike SARS-CoV-2 levels 6 months after two doses of BNT162b2 (Pfizer/Biotech) vaccine. Age and immunosuppressive therapy were the main predictors of humoral response to COVID-19 vaccine. We did not find any association between non-responders to HBV and non-responders to COVID-19 vaccine. There was no difference in IgG anti-spike titers between HBV responders and non-responders (505 ± 644 vs. 504 ± 781, p = 0.9) Our results suggest that reduced humoral response to hepatitis B is not associated with reduced response to COVID-19 vaccine. Different risk-factors were associated with poor immune response to HBV and to COVID-19 vaccines. Full article

Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets. Full article

Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with Engerix B^® lowers this risk by providing workers with immunity to the virus. However, through the years, we have encountered nonresponsive health personnel to the Engerix B^® vaccine; hence, the Occupational Health Service of Poniente Hospital studied the Fendrix^® adjuvanted vaccine as an alternative vaccine to develop immunological responses in healthcare workers who do not respond to vaccination with Engerix B^®. In our study, we employed a vaccination schedule with the Fendrix^® vaccine, performing serology tests on the cases after the application of each dose. The results obtained showed humoral immunity in 92.3% of the cases, with a remarkable increase in antibody titer after the first doses. These encouraging results support the future inclusion of this vaccine as one possible alternative for the immunization to HBV for healthcare workers nonresponsive to Engerix B^®. Full article