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As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2). [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of pseudolaric acid B (PAB) on the proliferation and apoptosis of HEp-2 cells. Methods Cell grouping and treatment: cells were treated with 0, 0.5, 1, 2, 4, 8 and 16 μmol/L PAB for 24, 48 and 72 h respectively; MTT assay was used to detect cell viability; flow cytometry was used to detect apoptosis; The expression of Bcl-2, Bax and caspase-3 protein and mRNA was detected by Western blot and qPCR. The expression of PARP and c-PARP was detected by immunohistochemistry. Results PAB inhibited HEp-2 proliferation in a time-concentration dependent manner. Compared with the control group, the apoptosis rate of HEp-2 cells in 4 μmol/L and 8 μmol/L PAB groups was significantly increased(P＜0.01). Compared with the control group, the expression of Bcl-2 and PARP in HEp-2 cells of 4 μmol/L and 8 μmol/L PAB groups were significantly decreased(P＜0.05), and the expression of Bax, caspase-3 and c-PARP was significantly increased(P＜0.05). Conclusions PAB can activate the mitochondrial apoptosis pathway thus induce apoptosis of HEp-2 cells and inhibit cell proliferation.

In order to study phylogeography, population dynamics and molecular evolution of rabies viruses (RABVs) isolates from China, especially spatio-temporal dynamics, the timescale of RABVs evolution and its pattern of migration, we performed an extensive comparative analysis of RABV N gene sequence data, representing 167 isolates sampled from 20 provinces in a 78-year period (from 1931 through 2009). The available Chinese isolates could be divided into two distinct clades:Phylogroup clades I comprised Chinese group 1-4; Phylogroup clades II contained Chinese group 5-8. We found no evidence for positive selection (dN/dS>1) acting at any codon and found strong selective constraints for N gene. Bayesian Markov Chain Monte Carlo (MCMC) analysis suggested that the Chinese rabies viruses originated within the last 2000 years and the mean rates of nucleotide substitution for the N gene were approximately 4 x 10(-4) substitutions per site per year. The analyses of the spatial and spatio-temporal evolution indicated that RABV isolates from China migrated among different Provinces.

Objective: Based on sequencing the genomes of glycoprotein (GP) gene of rabies viruses isolated in Zhejiang, we analyzed the properties of rabies viruses genetic variation in molecular level, and to compare with those of other representative vaccine strains and street virus strains, get the information about rabies viruses variation., Methods: Suckling mice against rabies virus were selected. Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses of the GP genes., Results: The fourteen full-length genomes were completely sequenced and they had the same genetic structure with 1575 nts and deduced protein with 524 aa. Genetic analysis revealed that the nucleotide and amino acid homologies of GP gene from Zhejiang strains and other vaccine strains or street virus strains were 82.3% - 99.9% and 85.1% - 99.8%. The fourteen strains were genotype 1 according to the phylogenetic analyses. The GP amino acids of Zhejiang strains rabies virus strains without any recombination occurred in GP and no larger variation appeared in the major antigenic sites., Conclusion: The comprehensive analysis based on the first-level structure of GP demonstrated that it was possible that some advantageous antigenic epitopes existed in certain areas and potential antigenic determinants. It was evident that the GP gene of Zhejiang strains appear to be stable and their sequence similarity with the representative strains of street virus in China were higher than those of other vaccine strains. Some differences showed in the genetic structure and evolution relationship among Zhejiang strains, other street strains in other regions and vaccine strains.

Based on sequencing the full-length genomes of four Chinese Ferret-Badger and dog, we analyze the properties of rabies viruses genetic variation in molecular level, get the information about rabies viruses prevalence and variation in Zhejiang, and enrich the genome database of rabies viruses street strains isolated from China. Rabies viruses in suckling mice were isolated, overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses from Chinese Ferret-Badger, dog, sika deer, vole, used vaccine strain were determined. The four full-length genomes were sequenced completely and had the same genetic structure with the length of 11, 923 nts or 11, 925 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions(IGRs), 423 nts-Pseudogene-like sequence (psi), 70 nts-Trailer. The four full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by BLAST and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the four full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so the nucleotide mutations happened in these four genomes were most synonymous mutations. Compared with the reference rabies viruses, the lengths of the five protein coding regions had no change, no recombination, only with a few point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the four genomes were similar to the reference vaccine or street strains. And the four strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessed the distinct district characteristics of China. Therefore, these four rabies viruses are likely to be street viruses already existing in the natural world.