Search Results (66)

The hepatitis C virus (HCV) is responsible for approximately 50 million infections worldwide. Effective drug treatments while available face access barriers, and vaccine development is hampered by viral hypervariability and immune evasion mechanisms. The CD4+ and CD8+ T-cell responses targeting HCV non-structural (NS) proteins have shown a role in the viral clearance. In this paper, we reviewed the studies exploring the relationship between HCV structural and NS proteins and their effects in contributing to the elicitation of an effective T-cell immune response. The use of different vaccine platforms, such as viral vectors and virus-like particles, underscores their versability and efficacy for vaccine development. Diverse HCV antigens demonstrated immunogenicity, eliciting a robust immune response, positioning them as promising vaccine candidates for protein/peptide-, DNA-, or RNA-based vaccines. Moreover, adjuvant selection plays a pivotal role in modulating the immune response. This review emphasizes the importance of HCV proteins and vaccination strategies in vaccine development. In particular, the NS proteins are the main focus, given their pivotal role in T-cell-mediated immunity and their sequence conservation, making them valuable vaccine targets. Full article

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(−) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk. Full article

Hepatitis E is a significant cause of acute hepatitis, contributing to high morbidity and mortality rates, and capable of causing large epidemics through fecal–oral transmission. Currently, no specific treatment for hepatitis E has been approved. Given the notably high mortality rate among HEV-infected pregnant women and individuals with underlying chronic liver disease, concerted efforts have been made to develop effective vaccines. The only licensed hepatitis E vaccine worldwide, the HEV 239 (Hecolin) vaccine, has been demonstrated to be safe and efficacious in Phase III clinical trials, in which the efficacy of three doses of HEV 239 remained at 86.6% (95% confidence interval (CI): 73.0–94.1) at the end of 10 years follow-up. In this review, the progress and challenges for hepatitis E vaccines are summarized. Full article

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010–2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010–2018. In 2015–2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs. Full article

Importance: Hepatitis B is a serious problem in the United States (US), with up to 2.4 million Americans living with a chronic infection. Only 26–32% of people living with hepatitis B in the US are diagnosed. Additionally, just 30% of all adults are vaccinated against the virus. In 2022, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) updated adult hepatitis B vaccination recommendations to include all adults aged 19–59 years and those 60 years and older with risk factors for hepatitis B. Subsequently, in 2023, the CDC recommended that all adults be screened at least one time in their lives. Observations: Electronic health record (EHR) tools (prompts, order sets, etc.) have proven to be an effective method of increasing hepatitis B screening and vaccination, but longstanding challenges and questions around hepatitis B vaccines and tests could prevent effectual EHR implementation. As the new recommendations directly impact providers who may have limited familiarity with hepatitis B, guidance on how to identify eligible patients and triggers, order sets to facilitate vaccine/test selection, and proper documentation and patient follow-up is necessary. Conclusions and Relevance: This communication offers a practical framework for health systems to build an effective EHR strategy for the updated adult hepatitis B recommendations. We also provide comprehensive responses to clinicians’ questions that are frequently asked prior to screening or vaccinating for hepatitis B. Full article

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991–1993 and in 1994–1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014–2021 was lower for regions that started adolescent vaccination in 1991–1993 rather than in 1994–1996 (IRR 0.76; 95% CI 0.72–0.83; p < 0.001). In the 20–29 age group, incidence in regions that started adolescent vaccination in 1991–1993 was also lower (IRR 0.87; 95% CI 0.77–0.98; p = 0.02 in 2005–2013 and IRR 0.71; 95% CI 0.56–0·90; p < 0.001 in 2014–2021). Anti-HBc prevalence in the 35–39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030. Full article

Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The hepatitis B vaccine has been used worldwide for more than four decades; it is available in a single- or triple-antigen form and in combination with vaccines against other infections. Introduction of the vaccine and administration at birth led to sustained decline in mother-to-child transmission, chronic hepatitis B, and HCC, however, global birth dose coverage remains suboptimal. In this review we will discuss different hepatitis B vaccine formulations and schedules, vaccination guidelines, durability of the response, and vaccine escape mutants, as well as the clinical and economic benefits of vaccination. Full article

Chronic infection with hepatitis B virus (HBV) develops in millions of patients per year, despite the availability of effective prophylactic vaccines. Patients who resolve acute HBV infection develop HBV-specific polyfunctional T cells accompanied by neutralizing antibodies, while in patients with chronic hepatitis B (CHB), immune cells are dysfunctional and impaired. We describe a lipid nanoparticle (LNP)-formulated mRNA vaccine, optimized for the expression of HBV core, polymerase, and surface (preS2-S) antigens with the aim of inducing an effective immune response in patients with CHB. Prime and prime/boost vaccination with LNP-formulated mRNA encoding for core, pol, and/or preS2-S dosing strategies were compared in naive C57BL/6 and BALB/c mice. Immune responses were assessed by IFN-γ ELISpot, intracellular cytokine staining (ICS), and ELISA for antibody production, whereas anti-viral efficacy was evaluated in the AAV-HBV mouse model. The mRNA vaccine induced strong antigen-specific polyfunctional T cell responses in these mouse models, accompanied by the emergence of anti-HBs and anti-HBe antibodies. After three immunizations, the antigen-specific immune stimulation resulted in up to 1.7 log₁₀ IU/mL reduction in systemic HBV surface antigen (HBsAg), accompanied by a transient drop in systemic HBeAg, and this was observed in 50% of the AAV-HBV-transduced mice in the absence of additional modalities such as adjuvants, HBsAg reducing agents, or checkpoint inhibitors. However, no treatment-related effect on viremia was observed in the liver. These results warrant further optimization and evaluation of this mRNA vaccine as a candidate in a multimodal therapeutic regimen for the treatment of chronic HBV infection. Full article

Within the past few decades, improvement in sanitation and economic growth has driven a changing epidemiology of hepatitis A in the Western Pacific Region (WPR) of the World Health Organization (WHO). In this review, we gathered available published information on hepatitis A epidemiology of the countries in the WPR and reviewed the trends reported in the literature from the years 2000 to 2021. Many countries have shifted from high endemicity to low endemicity. Moreover, the administration of the hepatitis A vaccine among children in recent years has shifted disease susceptibility to the older population. Seroprevalence among children has decreased in most countries, while nearly 100% seropositivity is seen in mid adulthood. This is contrary to the epidemiology seen in previous decades when most children achieved immunity by age ten. This also presents a paradox in that better living conditions have caused more vulnerability to the older age groups who are at higher risk for severe disease. Given these trends, we recommend vaccination of vulnerable populations such as the older age groups and inclusion of the hepatitis A vaccine in government immunization programs. Full article

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination. We used the calibrated model to evaluate the impact and costs of several childhood hepatitis A vaccination scenarios from 2023 to 2030. We assessed how each scenario impacted the burden of hepatitis A (symptomatic hepatitis A cases and mortality) as well as calculated the incremental cost per DALY averted as compared to the South African cost-effectiveness threshold. All costs and outcomes were discounted at 5%. For the modelled scenarios, the median estimated cost of the different vaccination strategies ranged from USD 1.71 billion to USD 2.85 billion over the period of 2023 to 2030, with the cost increasing for each successive scenario and approximately 39–52% of costs being due to vaccination. Scenario 1, which represented the administration of one dose of the hepatitis A vaccine in children < 2 years old, requires approximately 5.3 million vaccine doses over 2023–2030 and is projected to avert a total of 136,042 symptomatic cases [IQR: 88,842–221,483] and 31,106 [IQR: 22,975–36,742] deaths due to hepatitis A over the period of 2023 to 2030. The model projects that Scenario 1 would avert 8741 DALYs over the period of 2023 to 2030; however, it is not cost-effective against the South African cost-effectiveness threshold with an ICER per DALY averted of USD 21,006. While Scenario 3 and 4 included the administration of more vaccine doses and averted more symptomatic cases of hepatitis A, these scenarios were absolutely dominated owing to the population being infected before vaccination through the mass campaigns at older ages. The model was highly sensitive to variation of access to liver transplant in South Africa. When increasing the access to liver transplant to 100% for the baseline and Scenario 1, the ICER for Scenario 1 becomes cost-effective against the CET (ICER = USD 2425). Given these findings, we recommend further research is conducted to understand the access to liver transplants in South Africa and better estimate the cost of liver transplant care for hepatitis A patients. The modelling presented in this paper has been used to develop a user-friendly application for vaccine policy makers to further interrogate the model outcomes and consider the costs and benefits of introducing routine hepatitis A vaccination in South Africa. Full article

The hepatitis B virus is a public health threat, chronically infecting over 240 million persons worldwide. The hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 h of life, followed by a minimum of two subsequent doses. Antigua and Barbuda instituted a hospital-based birth dose vaccination policy in October 2021. Data were extracted from hospital logbooks from November 2021 to October 2022, and a database was created. Frequency distributions of the hepatitis B birth dose, barriers to administration, and maternal and healthcare system factors were analyzed. The positive maternal HBsAg prevalence rate was 0.6%. The timely and total birth dose coverage was 72% and 81%, respectively. In total, 10.5% of parents refused the vaccine, of which 76% either felt uncomfortable or preferred to wait. Moreover, 100% of hepatitis B-exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. Barriers to vaccine administration included vaccination hesitancy, gaps in knowledge of medical staff, and the inconsistent vaccination supply. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother-to-child transmission of hepatitis B by 2030 possible. Full article

Hepatitis B virus (HBV) infection is a global public health problem that is closely related to liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic HBV infection, liver cirrhosis, and HCC has significantly decreased as a result of the introduction of universal HBV vaccination programs. The first hepatitis B vaccine approved was developed by purifying the hepatitis B surface antigen (HBsAg) from the plasma of asymptomatic HBsAg carriers. Subsequently, recombinant DNA technology led to the development of the recombinant hepatitis B vaccine. Although there are already several licensed vaccines available for HBV infection, continuous research is essential to develop even more effective vaccines. Prophylactic hepatitis B vaccination has been important in the prevention of hepatitis B because it has effectively produced protective immunity against hepatitis B viral infection. Prophylactic vaccines only need to provoke neutralizing antibodies directed against the HBV envelop proteins, whereas therapeutic vaccines are most likely needed to induce a comprehensive T cell response and thus, should include other HBV antigens, such as HBV core and polymerase. The existing vaccines have proven to be highly effective in preventing HBV infection, but ongoing research aims to improve their efficacy, duration of protection, and accessibility. The routine administration of the HBV vaccine is safe and well-tolerated worldwide. The purpose of this type of immunization is to trigger an immunological response in the host, which will halt HBV replication. The clinical efficacy and safety of the HBV vaccine are affected by a number of immunological and clinical factors. However, this success is now in jeopardy due to the breakthrough infections caused by HBV variants with mutations in the S gene, high viral loads, and virus-induced immunosuppression. In this review, we describe various types of available HBV vaccines, along with the recent progress in the ongoing battle to develop new vaccines against HBV. Full article

Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. Full article

Motivations: Hepatitis B is a potentially life-threatening infectious disease caused by the hepatitis B virus (HBV). Approximately 390,000 people in China die from HBV-related diseases each year. Around 86 million individuals suffer from infections of the hepatitis B virus, accounting for about 6% of the total population in the region. There are approximately 30 million chronic infections. From 2002 to 2007, China’s government took part in “The Global Alliance for Vaccines and Immunization (GAVI)” initiative, which helped reduce cases of chronic HBV infections among children. However, incidences of hepatitis B remain persistently high in China. Accurately estimating the number of potential HBV infections is crucial for preventing and controlling the transmission of the hepatitis B virus. Up until now, there were no studies of potentially infectious hepatitis B virus infections. Methods: this study was based on data from the National Bureau of Statistics of China from 2003 to 2021; a dynamic model was built, which included a compartment for potentially infectious hepatitis B virus infections. The parameters in the model were fitted using a combination of nonlinear least-squares and genetic algorithm methods. Results: the calculated reproduction number for hepatitis B virus transmission within the population is Rc = 1.741. Considering the existing vaccine inefficiency rate of 0.1, the model estimates there are 449,535 (95%CI [415,651, 483,420]) potentially infectious hepatitis B virus infections, constituting 30.49% of total hepatitis B cases. Date fitting using MATLAB reveals that increasing the rate of hepatitis B vaccinations can effectively reduce the number of infections. Conclusions: the results reveal that the number of potential infectious hepatitis B virus infections is so high that the number of hepatitis B patients persistently rises in China. To better control the transmission of the hepatitis B virus, an optional prevention and control strategy is needed to increase the vaccination of different age groups, and it is necessary to help the public correctly understand the transmission of hepatitis B and ensure adequate protection. Full article

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5–10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders. Full article