Immune Response to Hepatitis B Virus Vaccine Among People Living With HIV: A Meta-Analysis

BackgroundThere is conflicting evidence about whether a double dose of the hepatitis B virus (HBV) vaccine induces better immunity than the standard-dose vaccine for people living with HIV (PLWH). This study provides a meta-analysis that summarizes the efficacy of HBV vaccine regimens among HIV-infected patients, clarifying the role of particular factors such as dose and frequency of vaccination in vaccine responsiveness and highlighting the need for evidence-based practice to assess HBV vaccination among PLWH.MethodsRandomized clinical trials (RCTs) and prospective studies reporting vaccination response rates among PLWH were found through a search of PubMed, Cochrane, and the Web of Science. The key outcome was vaccine response. A random-effects model was used to estimate the pooled response rate. Subgroup analysis was conducted to evaluate key factors and explore sources of heterogeneity. Possible biases were assessed using quality and publication bias assessment.ResultsEligible studies included controlled trials that examined the effects of 17 interventional studies with 1,821 participants. Among PLWH who received the HBV vaccine, the pooled response rate of HBV vaccination was 71.5% (95% CI 64.0%–77.9%, p < 0.001). Compared with the standard dose (65.5%, 95% CI 53.1%–76.1%), the double dose (75.2%, 95% CI 66.2%–82.5%) was associated with a better response rate [Q(1) = 19.617, p < 0.001]. When stratified by schedule, the four-dose schedule (89.7%, 95% CI 83.1%–93.9%) had a higher response rate than the three-dose schedule (63.3%, 95% CI 56.6%–69.4%) and the difference was significant [Q(1) = 88.305, p < 0.001]. PLWH with higher CD4+ T-cell counts (>500 cells/mm3) at the time of vaccination had better response rates [Q(1) = 88.305, p < 0.001].ConclusionsIn this meta-analysis, the double dose of the HBV vaccine and multiple injections were associated with better immune responses than the standard HBV vaccine regimen in PLWH. Higher seroconversion rates were observed in PLWH with high CD4+ T-cell levels, indicating that individuals infected with HIV should receive the HBV vaccine as soon as possible after diagnosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Undetectable Anti-HBs Antibodies: Need of a Booster Dose for HIV-1-Infected Individuals

HBV vaccination effectively prevents HBV transmission and the development of liver cancer. Disease progression and liver-related complications are more common in HIV-1/HBV co-infected than HBV mono-infected individuals. A considerable body of literature, which will be reviewed here, indicates that response to HBV vaccine is suboptimal in HIV-1-infected individuals and that the poor maintenance of protective immunity to HBV vaccines in these individuals is an important medical issue. Several factors affect HBV vaccine response during HIV-1 infection including CD4+ T cell counts, B cell response, vaccine formulation, schedules, and timing of antiretroviral therapy (ART). The initial response to HBV vaccination also plays a critical role in the sustainability of antibody responses in both HIV-1-infected and uninfected vaccinees. Thus, regular follow-up for antibody titer and a booster dose is warranted to prevent HBV transmission in HIV-1 infected people.

Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics

Despite the five decades having passed since discovery of the hepatitis B virus (HBV), together with development of an effective anti-HBV vaccine, infection with the virus remains a serious public health problem and results in nearly 900,000 annual deaths worldwide. Current therapies do not eliminate the virus and viral replication typically reactivates after treatment withdrawal. Hence, current endeavours are aimed at developing novel therapies to achieve a functional cure. Nucleic acid-based therapeutic approaches are promising, with several candidates showing excellent potencies in preclinical and early stages of clinical development. However, this class of therapeutics is yet to become part of standard anti-HBV treatment regimens. Obstacles delaying development of gene-based therapies include lack of clinically relevant delivery methods and a paucity of good animal models for preclinical characterisation. Recent studies have demonstrated safety and efficiency of Adeno-associated viral vectors (AAVs) in gene therapy. However, AAVs do have flaws and this has prompted research aimed at improving design of novel and artificially synthesised AAVs. Main goals are to improve liver transduction efficiencies and avoiding immune clearance. Application of AAVs to model HBV replication in vivo is also useful for characterising anti-HBV gene therapeutics. This review summarises recent advances in AAV engineering and their contributions to progress with anti-HBV gene therapy development.

Immunologic Response to Hepatitis B Virus Vaccination among Human Immunodeficiency Virus Thai Adults without Hepatitis B Virus Infection

Background: It is currently recommended that hepatitis B virus (HBV) vaccine be provided for every HIV-infected patient with no HBV immunity. HBV immunization program for HIV-infected patients was suggested to be given in three doses of vaccine at zero, one and six months. HBV vaccine has been included in the Thai immunization program for newborns for three doses, at birth, M2, and M6. Hence, one dose of vaccination might respond in complete protective immunity in some of the HIV patients. Objective: To evaluate HIV-infected patients’ response to one dose of vaccine and their associated factors. Materials and Methods: The present study was a Retrospective Cohort Study. It recruited patients who had come to Queen Savang Vadhana Memorial Hospital for their hepatitis B vaccination between January 1, 2018 and March 31, 2020. Eligible patients were infected with HIV, received ART, and had CD4 of more than 200 cells/mm³. The authors collected data from the patients having anti-HBs of less than 10 mIU/mL with negative anti-HBc who received HBV vaccine. From the medical records, the authors evaluated their anti-HBs titer after the first dose of vaccination, and the titer after a third dose, in cases the result of the first dose was negative. Results: Of the 88 HIV-infected patients who received HBV vaccination, 19 patients (21.6%) showed protective anti-HBs after the first dose of vaccination. Factors associated with the presence of anti-HBs after the first dose included age as the patients of 29 years or older had protective anti-HBs of 15% and the patients younger than 29 years old had protective anti-HBs of 43% (p=0.013), and anti-HBs titer before the vaccination as the patients with titer of less than 2 mIU/mL had protective anti-HBs of 17% and the patients with titer of 2 to less than 10 mIU/mL had protective anti-HBs of 44% (p=0.038). Conclusion: Some HIV-infected patients have developed protective anti-HBs after the first dose of HBV vaccination especially the younger age of less than 29 years old and with an anti-HBs titer before vaccination of 2 mlU/mL or above. Almost half of them required only one HBV booster to achieve protective anti-HBs. Keywords: Vaccine; Hepatitis B; HIV; Vaccination; Immunity

Hepatitis B Virus (HBV) Disease

HBV disease is a significant cause of acute and chronic liver disease worldwide. Mother-to-infant transmission is the main mode of transmission to susceptible subjects, which can be prevented with HBV vaccine alone or in combination with hepatitis B immunoglobulin. This intervention markedly reduces the number of new HBsAg carriers. For subjects not responding to current HBV vaccines as reflected by an inadequate anti-HBs titer, future generation vaccines incorporating additional vaccine components such as preS1 and preS2 may improve the efficacy of protective antibody production. Apart from preventative vaccines, future therapeutic vaccines along with current anti-HBV treatment strategies might enhance the rate of functional cures as indicated by the loss of HBsAg.

Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination.

The impact of the timely birth dose vaccine on the global elimination of hepatitis B

In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.

Low response rates to hepatitis B vaccine in patients with chronic hepatitis C

Background: Hepatitis B is an infectious disease with converging routes of transmission with hepatitis C, making vaccination important in hepatitis C infected people. The objective was to evaluate the vaccine response against hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV).Methods: Retrospective observational study was conducted between November 2018 and April 2020. Subjects with anti-HBs levels ≥10 mUI/ml were considered protected against HBV and those with chronic HCV who did not receive at least one dose of the vaccine schedule or with anti-HBc reagent or even with anti-HBs positive prior to the first dose documented in the HBV vaccine record were excluded. The immune response rates to VHB vaccine in patients with HCV was obtained and different variables were analysed.Results: The study group was compound of 370 subjects. The majority (55.7%) were male, with a median age of 55.6±11 years. Regarding present or past smoking, 56.9% of patients reported that were active or past tobacco users. HCV genotype 1 corresponded to 59.7% of the cases, followed by genotype 3 (36.88%). One hundred and fourteen (30.9%) of the patients had liver cirrhosis. The immune response to complete HBV vaccine was 62.3%, whereas the response to a single dose was 57.1% (p=1). Only the age of the patient at first dose (p=0.030), smoking status (p=0.017) and the presence of cirrhosis (p=0.046) influenced the immune response to HBV vaccine.Conclusions: The rate of immune response to standard schedule of HBV vaccination in patients with HCV was low (62.3%).

HCC and Molecular Targeting Therapies: Back to the Future

Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer in the world. Recently, the effectiveness of new antiviral therapies and the HBV vaccine have reduced HCC’s incidence, while non-alcoholic steato-hepatitis is an emerging risk factor. This review focuses on antiangiogenic molecules and immune checkpoint inhibitors approved for HCC treatment and possible future approaches. Sorafenib was the first drug approved for the treatment of advanced HCC (aHCC) and it has been shown to increase survival by a few months. Lenvatinib, a multikinase inhibitor, has shown non-inferiority in survival compared with sorafenib and an improvement in progression-free survival (PFS). The combination of atezolizumab (an anti-PDL1 antibody) and bevacizumab (an anti-VEGF antibody) was the first drug combination approved for HCC, demonstrating improved survival compared with sorafenib (19.2 vs. 13.4 months). As a second line of therapy, three regimens (regorafenib, cabozantinib, and ramucirumab) have been approved for the treatment of aHCC after progression on sorafenib according to guidelines. Furthermore, nivolumab, pembrolizumab, and nivolumab plus ipilimumab have been approved by the FDA (2017, 2018, and 2020, respectively). Finally, immune target therapy, cancer vaccines, and epigenetic drugs represent three new possible weapons for the treatment of HCC.

Hepatitis B vaccination status and associated factors among students of medicine and health sciences in Wolkite University, Southwest Ethiopia: A cross-sectional study

Background Hepatitis B virus (HBV) infection is a significant global public health problem. Health care providers and medical students in developing countries including Ethiopia are at an increased risk of contracting HBV due to the high burden of this infection. The most effective way of prevention against HBV infection is vaccination of health care providers. However, there is a paucity of data on the HBV vaccination coverage among students of health science in Ethiopia. Therefore, this study aimed to determine HBV vaccination coverage and associated factors, level of knowledge, attitudes, and practices (KAP) towards HBV among students of medicine and health science at Wolkite University. Materials and methods A cross-sectional study was conducted at Wolkite University among 417 study participants from November to December 2020. The study participants were recruited by using a simple random sampling technique. Data were collected using a self-administered structured questionnaire and analyzed using SPSS version 21. A binary logistic regression model was used to determine the factors associated with full-dose vaccination status. Statistical significance was set at P-value <0.05. Results Out of the 417 study participants, 5.8% (95%CI: 3.8–7.9) received a full-dose of the HBV vaccine in this study. Unavailability and high cost of the vaccine were frequently mentioned reasons for not being vaccinated against HBV. About 73.6%, 36.2%, and 47% of participants had good knowledge, positive attitudes, and good practices towards HBV, respectively. Being male gender (AOR: 8.8; 95%CI: 2.9–27), rural residence (AOR: 3.6; 95%CI:1.2–10.6), positive attitude (AOR: 0.44; 95%CI: 0.1–1.1), good practice (AOR: 0.17; 95%CI: 0.05–0.5), medicine department (AOR: 5.9; 95%CI: 1.2–29), being second-year student (AOR: 11.7; 95%CI: 2.7–50.9), third-year student (AOR: 19; 95%CI: 4.25–45), and fourth-year student (AOR: 27; 95%CI: 5.8–56) were significantly associated factors with full-dose vaccination status. Conclusion Our study revealed that only small proportions (5.8%) of study participants received full-dose HBV vaccination. Vaccinations of students before starting clinical attachments, provisions of training for students on infection prevention mechanism and universal precautions particularly on HBV, increasing the uptake of the HBV vaccine, creating awareness on attitude and practice of students towards HBV to enhance uptake of the vaccine are recommended.