Design and development of a chimeric vaccine candidate against zoonotic hepatitis E and foot-and-mouth disease.

BACKGROUND: Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries. The aim of this study is exploring a new approach for the control of zoonotic HEV in its main host (swine) through the design and development of an economically interesting chimeric vaccine against HEV and against a devastating swine infection: the foot-and-mouth disease virus (FMDV) infection. RESULTS: First, we adopted a computational approach for rational and effective screening of the different HEV-FMDV chimeric proteins. Next, we further expressed and purified the selected chimeric immunogens in Escherichia coli (E. coli) using molecular cloning techniques. Finally, we assessed the antigenicity and immunogenicity profiles of the chimeric vaccine candidates. Following this methodology, we designed and successfully produced an HEV-FMDV chimeric vaccine candidate (Seq 8-P222) that was highly over-expressed in E. coli as a soluble protein and could self-assemble into virus-like particles. Moreover, the vaccine candidate was thermo-stable and exhibited optimal antigenicity and immunogenicity properties. CONCLUSION: This study provides new insights into the vaccine development technology by using bioinformatics for the selection of the best candidates from larger sets prior to experimentation. It also presents the first HEV-FMDV chimeric protein produced in E. coli as a promising chimeric vaccine candidate that could participate in reducing the transmission of zoonotic HEV to humans while preventing the highly contagious foot-and-mouth disease in swine.

Unimpaired immunogenicity of yeast-expressed hepatitis B surface antigen stored at elevated temperatures.

Global adoption of hepatitis B virus (HBV) vaccines has greatly reduced new HBV infections. Current HBV vaccines are liquid suspensions containing recombinant hepatitis B surface antigen (HBsAg) particles mixed with aluminum phosphate or aluminum hydroxide. Refrigeration (2-8°C) as recommended for vaccine transport and storage may be unachievable in certain HBV-prevalent developing countries or regions. In this study, we stored yeast-expressed HBsAg and aluminum hydroxide separately at the standard (4°C) and elevated temperature (25, 37, or 45°C) for 14, 23, and 30 days, then mixed them and used the mixture to vaccinate mice with a prime-boost program. The antisera from all the vaccinated mice successfully inhibited HBV infection of HepG2 cells stably expressing HBV receptor sodium taurocholate cotransporting polypeptide. Furthermore, no serum HBsAg was detected in vaccinated mice on Day 1 post-hydrodynamic injection (HDI) of an HBV replicon plasmid and onwards, accompanied with an increasing anti-HBsAg antibody (HBsAb) level. In contrast, serum HBsAg in phosphate-buffered saline (PBS)-injected mice peaked on Day 4 post-HDI and was cleared on Day 14 post-HDI, which coincided with appearance of HBsAb on Day 7 post-HDI, suggesting a typical HBV acute infection process. HBV DNA peaked on Day 4 post-HDI in vaccinated mice, its level significantly lower than that in PBS-injected mice on Day 7 post-HDI, and showed a higher clearance rate. Taken together, we conclude that storing recombinant HBsAg at 25, 37, or 45°C for 14-30 days does not impair its immunogenicity in mice.

[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

Hepatitis C virus genotype diversity in Shanghai, China.

We studied 67 hepatitis C virus (HCV) isolates from 64 hospitalized patients in Shanghai, China. Genotype 1 was prevalent, and genotypes 2, 3, 6 were found for the first time in Shanghai. A rare mixed infection with three subtypes (1a, 1b, 2a) was found. The complete genome sequence of a subtype 3b isolate was determined and analyzed.