Tao Sun

The goal of the next‐generation COVID‐19 vaccine is to provide rapid respiratory tract protection with a single dose. Circulating antibodies do not protect the olfactory mucosa from viral infection, necessitating localized mucosal immunization. Live attenuated vesicular stomatitis virus (VSV _MT )‐based COVID‐19 vaccines effectively stimulate mucosal immunity in animals, though safety concerns remain, particularly in immunocompromised populations. A viral vector capable of single‐cycle replication may face less stringent regulatory requirements. A replication‐defective VSV _MT is developed with its G protein replaced by a SARS‐CoV‐2 spike protein (S) mutant, where residues K986 and V987 are substituted by prolines (S2P). This studies show that single‐cycle VSV _MT encoding Omicron subvariant S2P (VSV _MT ‐S2P) is safe in both healthy and immunocompromised animals treated with cyclophosphamide (CP). Significant antibody and T‐cell responses against the spike protein are observed in VSV _MT ‐S2P vaccinated healthy animals. Intramuscular VSV _MT ‐S2P administration induces neutralizing antibody responses comparable to those from replication‐competent VSV _MT ‐S. In immunocompromised animals, lower and delayed immune responses are observed. Thus, single‐cycle M‐protein mutated VSV offers a safe and effective platform for SARS‐CoV‐2 immunogen delivery. Remarkably, replication‐competent VSV _MT ‐S caused no pathogenicity and elicited potent mucosal immunity via intranasal administration, highlighting its potential as a mucosal COVID‐19 vaccine.

The Omicron variant has swept through most countries and become a dominant circulating strain, replacing the Delta variant. The evolutionary history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that the onset of another variant (possibly another variant of concern (VOC) is inevitable. Therefore, the development of therapeutics that enable treatments for all Omicron-included VOCs/variants of interest (VOIs) and future variants is desired. Recently, the recombinant receptor decoy therapeutic angiotensin-converting enzyme 2 (ACE2)-Fc has exhibited good safety in a phase 1 clinical trial; therefore, its variant-resistant profile needs to be understood. Here, we conducted a comprehensive evaluation of its neutralization breadth against the Omicron variant and other VOCs/VOIs. Furthermore, to evaluate its resistance to future variants, we investigated its ability to neutralize various single-residue mutated variants. Next, we demonstrated its resistance to evasion via an experiment that rapidly and effectively stimulates virus evolution with a replication-competent virus model. In addition, we evaluated its efficacy for cocktail therapy. The combination of ACE2-Fc and neutralizing antibodies showed both efficacy and breadth in the simulation experiment. The underlying mechanism was revealed to be a synergistic effect in the cocktails. Collectively, this study deepens the understanding of the resistance profile of recombinant receptor decoy therapeutics and highlights the potential value of ACE2-Fc and neutralizing antibody cocktails in the subsequent anti-SARS-CoV-2 campaign. Furthermore, we also provide an effective method to study the resistance profile of antiviral agents and rapidly screen for potential cocktails to combat future variants.

The consumption of cheese in China is increasing rapidly. Little is known about the microbiota, the presence of antibiotic-resistant bacteria, or the distribution of antibiotic resistance genes (ARGs) in commercially-produced cheeses sold in China. These are important criteria for evaluating quality and safety. Thus, this study assessed the metagenomics of fifteen types of cheese using 16S rRNA gene sequencing. Fourteen bacterial genera were detected. Lactococcus , Lactobacillus , and Streptococcus were dominant based on numbers of sequence reads. Multidrug-resistant lactic acid bacteria were isolated from most of the types of cheese. The isolates showed 100% and 91.7% resistance to streptomycin and sulfamethoxazole, respectively, and genes involved in acquired resistance to streptomycin ( strB) and sulfonamides ( sul2) were detected with high frequency. To analyze the distribution of ARGs in the cheeses in overall, 309 ARGs from eight categories of ARG and nine transposase genes were profiled. A total of 169 ARGs were detected in the 15 cheeses; their occurrence and abundance varied significantly between cheeses. Our study demonstrates that there is various diversity of the bacteria and ARGs in cheeses sold in China. The risks associated with multidrug resistance of dominant lactic acid bacteria are of great concern.

Porcine epidemic diarrhea (PED) is a devastating disease in livestock industry. Most of the previous studies related to the PED were focused on the pathology and etiology of porcine epidemic diarrhea virus (PEDV). A little was known regarding the status of gut microbiota after piglets infected by PEDV. In this study, aided by metagenome sequencing technology, gut microbiota profiles in feces of viral diarrhea (VD) and viral control (VC) piglets were investigated. The results showed that the abundance of four dominant phyla (Fusobacteria, Actinobacteria, Verrucomicrobia, and Proteobacteria) in feces was affected greatly by porcine epidemic diarrhea. Especially, the abundance of Fusobacteria was higher in VD piglets (36 %) than in VC piglets (5 %). On the contrary, the Verrucomicrobia was detected in lower distribution proportion in VD piglets (around 0 %) than in VC piglets (20 %). Furthermore, 25 genera were significantly different between VC and VD piglets at the genus level. Among the 25 genera, Leptotrichia belonging to Fusobacteria was remarkably lower in VC piglets than in VD piglets. Akkermansia belonging to Verrucomicrobia was higher in VC piglets than in VD piglets. Our findings implicated that the gut microbiota associated with PED significantly provided an insight into the pathology and physiology of PED.