New facet of CARs: HBV-specific CARs as inhibitors of virus morphogenesis and release

Although safe and effective vaccines against HBV (hepatitis B virus) are available, there are worldwide more than 2 billion people who had an HBV infection and about 250 million people suffering from chronic HBV infection. Chronic HBV infection is a major cause for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It is estimated that about 800 000–1 000 000 people die each year due to the consequences of chronic HBV infection.1 Moreover, in almost all HBV-associated HCCs integrated HBV-DNA is found. Therapy options at present are limited and based on nucleoside/nucleotide analogues and interferon alpha. Since persistence of HBV infection frequently can be attributed to an insufficient cellular immune response approaches to rescue host immune response may help to eliminate infected cells and to suppress virus replication. A recent development are HBV-specific CARs (chimeric antigen receptors) human T-cells that are intended to recognise and eliminate HBV positive…

Leggi
Marzo 2024

Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study

Objectives
This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia.

Design
A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals.

Setting
All administrative units of Armenia including 10 provinces and capital city Yerevan.

Participants
The study frame was the general adult population of Armenia aged ≥18 years.

Primary and secondary outcome measures
The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models.

Results
The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93).

Conclusion
This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

Leggi
Febbraio 2024

Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study

Introduction
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.

Method
Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.

Analysis
Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.

Ethics
National Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.

Dissemination
Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

Leggi
Febbraio 2024

Abstract TMP8: Varicella Zoster Virus Infection in Children With Arterial Ischemic Stroke: The Chicken or the Egg?

Stroke, Volume 55, Issue Suppl_1, Page ATMP8-ATMP8, February 1, 2024. Introduction:Serologic evidence of varicella zoster virus (VZV) infection has been associated with childhood arterial ischemic stroke (AIS). Questions of causality persist: does VZV infection cause AIS, or does AIS reactivate VZV? The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to examine this relationship.Methods:This North American 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022). Blood samples were hyperacute (≤72hrs; n=194), acute (4-7 days; n=180) and convalescent (1-6 weeks; n=73). A virology research lab used ELISA to measure VZV IgM and IgG titers. A pediatric virologist (CG) interpreted the results and classified the evidence of infection. Low-level IgG seropositivity is consistent with prior vaccination/infection. Highly elevated IgM in hyperacute/acute samples indicatedreactivationcoincident withstroke. Rising IgG titers between hyperacute and convalescent samples, occasionally with a high IgM in convalescent sample, indicatedreactivationafterthe stroke.Results:Median age (IQR) was 11.6 years (5.3, 15.6). All 205 cases were low-level IgG positive; 160 (78%) reported prior VZV vaccination and 3 reported remote chicken pox. Serologies for 15 (7.3%; 95% CI 4.1, 11.8%) indicated VZV reactivation coincident with stroke; prior VZV vaccination reported in 14 and unknown in one. Stroke etiology amongst these 15 was definite arteriopathy in 4 (27%), possible arteriopathy in 4 (27%), cardioembolic in 5 (33%), and idiopathic in 2 (13%) (compared to 37%, 37%, 10%, 14%, respectively, for the other 190). Among 73 with convalescent samples, 17 (23%) had VZV reactivation after stroke. All cases of VZV reactivation were asymptomaticzoster sine herpete(herpes zoster without rash).Conclusions:While stroke triggered VZV reactivation in 23% of cases, 7.3% had evidence ofzoster sine herpeteat the time of their stroke, implying a causal role. We could not distinguish antibodies to vaccine virus versus wild-type; these zoster cases could represent reactivation of vaccine virus or a break-through wild-type varicella infection. Either scenario would be unexpected in this current era of routine childhood VZV vaccination and low rates of pediatric chicken pox or zoster.

Leggi
Febbraio 2024

Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model

Objectives
Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.

Methods
We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).

Results
Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.

Conclusions
We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.

Leggi
Gennaio 2024

Live-Virus Shingles Vaccine Provided Some Long-Term Protection

New results suggest that a live-virus vaccine intended to protect against shingles—a condition caused by reactivation of the varicella-zoster virus, which also causes chickenpox—prevented illness in 67% of people in the first year after vaccination. But after 10 years, the vaccine’s efficacy against shingles, also known as herpes zoster, had declined to 15%. The study used electronic health record data from more than 500 000 adults aged 50 years or older who received the shot between 2007 and 2018 in California.

Leggi
Dicembre 2023