Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.

Background: Hospital staff are at high risk of infection during the coronavirus disease (COVID-19) pandemic. We analysed the exposure characteristics, efficacy of protective measures, and transmission dynamics in this hospital-wide prospective seroprevalence study. Methods and Findings: Overall, 4554 individuals were tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies using a chemiluminescent immunoassay. Individual risk factors, use of personal protective equipment (PPE), occupational exposure, previous SARS-CoV-2 infection, and symptoms were assessed using a questionnaire and correlated to anti-SARS-CoV-2 IgG antibody titres and PCR testing results. Odds ratios with corresponding exact 95% confidence intervals were used to evaluate associations between individual factors and seropositivity. Spatio-temporal trajectories of SARS-CoV-2-infected patients and staff mobility within the hospital were visualised to identify local hotspots of virus transmission. The overall seroprevalence of anti-SARS-CoV-2-IgG antibody was 2.4% [95% CI 1.9–2.9]. Patient-facing staff, including those working in COVID-19 areas, had a similar probability of being seropositive as non-patient-facing staff. Prior interaction with SARS-CoV-2-infected co-workers or private contacts and unprotected exposure to COVID-19 patients increased the probability of seropositivity. Loss of smell and taste had the highest positive predictive value for seropositivity. The rate of asymptomatic SARS-CoV-2 infections was 25.9%, and higher anti-SARS-CoV-2 IgG antibody titres were observed in symptomatic individuals. Spatio-temporal hotspots of SARS-CoV-2-positive staff and patients only showed partial overlap. Conclusions: Patient-facing work in a healthcare facility during the SARS-CoV-2 pandemic may be safe if adequate PPE and hygiene measures are applied. The high numbers of asymptomatic SARS-CoV-2 infections that escaped detection by symptomatic testing underline the value of cross-sectional seroprevalence studies. Unprotected contact is a major risk factor for infection and argues for the rigorous implementation of hygiene measures.

Objectives: The VaCoMRI study tracked a cohort of healthcare workers from 2020 through June 2024 to characterize the long-term sustainability of hybrid and vaccine-induced SARS-CoV-2 immunity. Methods: An initial anti-nucleocapsid (N) IgG screening of 4554 health-care workers in early 2020 identified participants who had been infected during the first wave. Anti-N-positive and anti-N-negative individuals then received BNT162b2 through the institutional vaccination program, yielding groups with hybrid and vaccine-induced immunity. Both groups were monitored regularly for nearly four years for breakthrough infections (BTI). Serum collected regularly after vaccination and after BTI was analyzed for anti-N, quantitative anti-spike (anti-S) IgG, and surrogate viral neutralizing antibody (sVNT) titers. Results: Over a median follow-up of 1180 days, 142 healthcare workers contributed longitudinal samples; 66.2% experienced one BTI and 14.1% a second. In initially seronegative individuals, anti-N titers decreased 2.3-fold between 3 and 6 months after the first BTI, with seropositivity dropping from 82% to 40.4% (median time to seronegativity: 179 days). Prior anti-N seropositivity was associated with 4.5-fold higher anti-N IgG levels after BTI, with elevated levels persisting through 9 months. In both groups, the third vaccine dose significantly enhanced anti-S antibody persistence after 9 months compared to the second dose. In infection-naïve individuals, anti-S IgG titers remained 4.2-fold and sVNT titers 7.2-fold higher. Hybrid immunity was similarly durable: two vaccine doses after prior anti-N seropositivity yielded anti-S IgG and sVNT levels comparable to three-dose vaccination. Conclusions: This study demonstrates a rapid waning of anti-N IgG that severely limits its reliability for retrospective serosurveillance of SARS-CoV-2 exposure in occupational settings. The combination of vaccination and infection induced robust and durable spike-directed antibody responses. However, these were determined using assays based on the ancestral spike protein. This may limit the prediction of protection from SARS-CoV-2 variants, which usually cause BTIs.