Induction of Hepatitis E Virus Anti-ORF3 Antibodies from Systemic Administration of a Muscle-Specific Adeno-Associated Virus (AAV) Vector.

The hepatitis E virus (HEV) is a major global health problem, leading to large outbreaks in the developing world and chronic infections in the developed world. HEV is a non-enveloped virus, which circulates in the blood in a quasi-enveloped form. The quasi-envelope protects HEV particles from neutralising anti-capsid antibodies in the serum; however, most vaccine approaches are designed to induce an immune response against the HEV capsid. In this study, we explored systemic in vivo administration of a novel synthetic and myotropic Adeno-associated virus vector (AAVMYO3) to express the small HEV phosphoprotein ORF3 (found on quasi-enveloped HEV) in the musculature of mice, resulting in the robust and dose-dependent formation of anti-ORF3 antibodies. Neutralisation assays using the serum of ORF3 AAV-transduced mice showed a modest inhibitory effect on the infection of quasi-enveloped HEV in vivo, comparable to previously characterised anti-ORF3 antibodies used as a control. The novel AAVMYO3 capsid used in this study can serve as a versatile platform for the continued development of vector-based vaccines against HEV and other infectious agents, which could complement traditional vaccines akin to the current positive experience with SARS-CoV-2.

Hepatitis E in Bangladesh: Insights From a National Serosurvey.

BACKGROUND: Hepatitis E virus (HEV) genotypes 1 and 2 are a major cause of avoidable morbidity and mortality in South Asia. Despite the high risk of death among infected pregnant women, scarce incidence data has been a contributing factor to global policy recommendations against the introduction of licensed hepatitis E vaccines, one of the only effective prevention tools. METHODS: We tested serum from a nationally representative serosurvey in Bangladesh for anti-HEV immunoglobulin G and estimated seroprevalence. We used Bayesian geostatistical models to generate high-resolution maps of seropositivity and examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression. RESULTS: We tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of 20% (95% confidence interval [CI], 17%-24%). Seropositivity increased with age and male sex (odds ratio, 2.2 male vs female; 95% CI, 1.8-2.8). Community-level seroprevalence ranged widely (0-78%) with higher seroprevalence in urban areas, including Dhaka, with a 3.0-fold (95% credible interval, 2.3-3.7) higher seroprevalence than the rest of the country. CONCLUSIONS: Hepatitis E infections are common throughout Bangladesh. Strengthening surveillance for hepatitis E, especially in urban areas, can provide additional evidence to appropriately target interventions.

Natural antiviral compound silvestrol modulates human monocyte-derived macrophages and dendritic cells.

Outbreaks of infections with viruses like Sars-CoV-2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona-, Ebola-, Zika-, Picorna-, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down-regulated several pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, CCL2, CCL18) and increased TNF-α during differentiation and activation of M1-macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti-inflammatory potential of M2-macrophages by increasing expression of anti-inflammatory surface markers CD206, TREM2 and reducing release of pro-inflammatory IL-8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down-regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status.