A novel T cell–based ZIKV vaccine, encoding NS1 protein, confers protection against systemic infection.

Background: Screening of transfusion-transmissible infections (TTIs) among blood donors can be a cost-effective approach to monitor the prevalence, distribution, and trends of the infections among healthy-looking individuals. The study aimed to determine the seroprevalence of four TTIs, human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis, among blood donors in Kathmandu, Nepal. Methodology: A total of 21,716 units of blood were tested for the presence of anti-HIV 1/2 IgG/IgM, HBsAg, anti-HCV IgG/IgM, and anti-Treponema pallidum IgG/IgM/IgA using commercial ELISA kits following standard protocols. Statistical analysis was performed using WinPepi Ver 3.8. Results: Seroprevalence of HIV, HBV (HBsAg), HCV and syphilis were observed to be 0.12% (95% CI = 0.08-0.18), 0.47% (95% CI = 0.39-0.57), 0.64% (95% CI = 0.54-0.75) and 0.48% (95% CI = 0.40-0.59) respectively. TTIs were dominant among male blood donors compared to female blood donors. Higher HCV seroprevalence among males compared to females was statistically significant. HIV prevalence was highest among blood donors in the age group 31 to 40 years (P > 0.5). HBV, HCV and syphilis prevalence was highest among blood donors 41 to 50 years age group, 21 to 30 years age group, and 51 to 60 years age group respectively (P < 0.05). HIV and HBV prevalence was relatively higher among first-time donors, whereas HCV and syphilis was relatively higher among the repeated donors (P > 0.05). Conclusions: It is of utmost importance to continue screening donated blood with highly sensitive and specific tests and to counsel donors who are positive to any of the above infections. It is absolutely necessary to avoid the transmission of infection from repeat donors.

As one of the causative agents of viral hepatitis, hepatitis E virus (HEV) has gained public health attention globally. HEV epidemics occur in developing countries, associated with faecal contamination of water and poor sanitation. In industrialised nations, HEV infections are associated with travel to countries endemic for HEV, however, autochthonous infections, mainly through zoonotic transmission, are increasingly being reported. HEV can also be transmitted by blood transfusion. Nepal has experienced a number of HEV outbreaks, and recent earthquakes resulted in predictions raising the risk of an HEV outbreak to very high. This study aimed to measure HEV exposure in Nepalese blood donors after large earthquakes. Samples (n = 1,845) were collected from blood donors from Kathmandu, Chitwan, Bhaktapur and Kavre. Demographic details, including age and sex along with possible risk factors associated with HEV exposure were collected via a study-specific questionnaire. Samples were tested for HEV IgM, IgG and antigen. The proportion of donors positive for HEV IgM or IgG was calculated overall, and for each of the variables studied. Chi square and regression analyses were performed to identify factors associated with HEV exposure. Of the donors residing in earthquake affected regions (Kathmandu, Bhaktapur and Kavre), 3.2% (54/1,686; 95% CI 2.7–4.0%) were HEV IgM positive and two donors were positive for HEV antigen. Overall, 41.9% (773/1,845; 95% CI 39.7–44.2%) of donors were HEV IgG positive, with regional variation observed. Higher HEV IgG and IgM prevalence was observed in donors who reported eating pork, likely an indicator of zoonotic transmission. Previous exposure to HEV in Nepalese blood donors is relatively high. Detection of recent markers of HEV infection in healthy donors suggests recent asymptomatic HEV infection and therefore transfusion-transmission in vulnerable patients is a risk in Nepal. Surprisingly, this study did not provide evidence of a large HEV outbreak following the devastating earthquakes in 2015.

Hepatitis C virus (HCV) is a significant contributor to the global disease burden, and development of an effective vaccine is required to eliminate HCV infections worldwide. CD4⁺ and CD8⁺ T cell immunity correlates with viral clearance in primary HCV infection, and intrahepatic CD8⁺ tissue-resident memory T (T_RM) cells provide lifelong and rapid protection against hepatotropic pathogens. Consequently, we aimed to develop a vaccine to elicit HCV-specific CD4⁺ and CD8⁺ T cells, including CD8⁺ T_RM cells, in the liver, given that HCV primarily infects hepatocytes. To achieve this, we vaccinated wild-type BALB/c mice with a highly immunogenic cytolytic DNA vaccine encoding a model HCV (genotype 3a) nonstructural protein (NS5B) and a mutant perforin (pVAX-NS5B-PRF), as well as a recombinant adeno-associated virus (AAV) encoding NS5B (rAAV-NS5B). A novel fluorescent target array (FTA) was used to map immunodominant CD4⁺ T helper (T_H) cell and cytotoxic CD8⁺ T cell epitopes of NS5B in vivo, which were subsequently used to design a K^dNS5B_451-459 tetramer and analyze NS5B-specific T cell responses in vaccinated mice in vivo. The data showed that intradermal prime/boost vaccination with pVAX-NS5B-PRF was effective in eliciting T_H and cytotoxic CD8⁺ T cell responses and intrahepatic CD8⁺ T_RM cells, but a single intravenous dose of hepatotropic rAAV-NS5B was significantly more effective. As a T-cell-based vaccine against HCV should ideally result in localized T cell responses in the liver, this study describes primary observations in the context of HCV vaccination that can be used to achieve this goal. IMPORTANCE There are currently at least 71 million individuals with chronic HCV worldwide and almost two million new infections annually. Although the advent of direct-acting antivirals (DAAs) offers highly effective therapy, considerable remaining challenges argue against reliance on DAAs for HCV elimination, including high drug cost, poorly developed health infrastructure, low screening rates, and significant reinfection rates. Accordingly, development of an effective vaccine is crucial to HCV elimination. An HCV vaccine that elicits T cell immunity in the liver will be highly protective for the following reasons: (i) T cell responses against nonstructural proteins of the virus are associated with clearance of primary infection, and (ii) long-lived liver-resident T cells alone can protect against malaria infection of hepatocytes. Thus, in this study we exploit promising vaccination platforms to highlight strategies that can be used to evoke highly functional and long-lived T cell responses in the liver for protection against HCV.