The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

The impact of exercise on the gut microbiota in middle-aged amateur serious runners: a comparative study.

Introduction: Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultra-marathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals. Methods: We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire. Results and Discussion: Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in ß diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation.

Structural characteristics of gut microbiota in longevity from Changshou town, Hubei, China.

The gut microbiota (GM) and its potential functions play a crucial role in maintaining host health and longevity. The aim of this study was to investigate the potential relationship between GM and longevity. We collected fecal samples from 92 healthy volunteers (middle-aged and elderly: 43-79 years old; longevity: ≥ 90 years old) from Changshou Town, Zhongxiang City, Hubei, China. In addition, we collected samples from 30 healthy middle-aged and elderly controls (aged 51-70 years) from Wuhan, Hubei. The 16S rDNA V3 + V4 region of the fecal samples was sequenced using high-throughput sequencing technology. Diversity analysis results showed that the elderly group with longevity and the elderly group with low body mass index (BMI) exhibited higher α diversity. However, no significant difference was observed in ß diversity. The results of the microbiome composition indicate that Firmicutes, Proteobacteria, and Bacteroidota are the core phyla in all groups. Compared to younger elderly individuals, Akkermansia and Lactobacillus are significantly enriched in the long-lived elderly group, while Megamonas is significantly reduced. In addition, a high abundance of Akkermansia is a significant characteristic of elderly populations with low BMI values. Furthermore, the functional prediction results showed that the elderly longevity group had higher abilities in short-chain fatty acid metabolism, amino acid metabolism, and xenobiotic biodegradation. Taken together, our study provides characteristic information on GM in the long-lived elderly population in Changshou Town. This study can serve as a valuable addition to the current research on age-related GM. KEY POINTS: • The gut microbiota of elderly individuals with longevity and low BMI exhibit higher alpha diversity • Gut microbiota diversity did not differ significantly between genders in the elderly population • Several potentially beneficial bacteria (e.g., Akkermansia and Lactobacillus) are enriched in long-lived individuals.

30-Year Development of Inactivated Virus Vaccine in China.

Inactivated vaccines are vaccines made from inactivated pathogens, typically achieved by using chemical or physical methods to destroy the virus's ability to replicate. This type of vaccine can induce the immune system to produce an immune response against specific pathogens, thus protecting the body from infection. In China, the manufacturing of inactivated vaccines has a long history and holds significant importance among all the vaccines available in the country. This type of vaccine is widely used in the prevention and control of infectious diseases. China is dedicated to conducting research on new inactivated vaccines, actively promoting the large-scale production of inactivated vaccines, and continuously improving production technology and quality management. These efforts enable China to meet the domestic demand for inactivated vaccines and gain a certain competitive advantage in the international market. In the future, China will continue to devote itself to the research and production of inactivated vaccines, further enhancing the population's health levels and contributing to social development. This study presents a comprehensive overview of the 30-year evolution of inactivated virus vaccines in China, serving as a reference for the development and production of such vaccines.

Safety and immunogenicity of rabies vaccine (PVRV-WIBP) in healthy Chinese aged 10-50 years old: Randomized, blinded, parallel controlled phase III clinical study.

This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10-50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10-50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.

Development of an Antigen Detection Kit Capable of Discriminating the Omicron Mutants of SARS-CoV-2.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world, caused millions of deaths and a severe illness which poses a serious threat to human health. OBJECTIVE: To develop an antigen detection kit that can identify Omicron novel coronavirus mutants. METHODS: BALB/c mice were immunized with the nucleocapsid protein of SARS-CoV-2 Omicron mutant treated with ß-propiolactone. After fusion of myeloma cells with immune cells, Elisa was used to screen the cell lines capable of producing monoclonal antibodies. The detection kit was prepared by colloidal gold immunochromatography. Finally, the sensitivity, specificity and anti-interference of the kit were evaluated by simulating positive samples. RESULTS: The sensitivity of the SARS-CoV-2 antigen detection kit can reach 62.5 TCID50/mL, and it has good inclusiveness for different SARS-CoV-2 strains. The kit had no cross-reaction with common respiratory pathogens, and its sensitivity was still not affected under the action of different concentrations of interferences, indicating that it had good specificity and stability. CONCLUSION: In this study, monoclonal antibodies with high specificity to the N protein of the Omicron mutant strain were obtained by monoclonal antibody screening technology. Colloidal gold immunochromatography technology was used to prepare an antigen detection kit with high sensitivity to detect and identify the mutant Omicron strain.

Safety and immunogenicity of a quadrivalent, inactivated, split-virion influenza vaccine (IIV4-W) in healthy people aged 3-60 years: a phase III randomized clinical noninferiority trial.

BACKGROUND: A quadrivalent split influenza vaccine IIV4-W against both influenza A and B viruses is urgently needed. METHODS: To evaluate the safety and immunogenicity of IIV4-W in people aged 3-60 years, 2400 participants recruited in a double-blind phase III trial and were randomly assigned to the IIV4-W, TIV1 and TIV2 groups. The immunogenicity indicators were measured at 28 days postvaccination and for 180 days for safety follow-up. RESULTS: Adverse events (AEs) occurred in 162 (20.28%), 116 (14.55%) and 123 (15.41%) participants in the IIV4-W, TIV1 and TIV2 groups, respectively. All these AEs were mild and self-limiting, and no serious AEs related to the vaccines were observed. IIV4-W elicited a non-inferior immune response for matched strains (the lower limit of 95% CI for GMT ratio >0.67, for SCR and SPR difference >-10%) and superior immune response for the additional B strains (the lower limit of 95% CI for GMT ratio >1.5, for SCR difference >10%) versus TIVs. The lower limit of the 95% confidence interval of the GMT increase fold, the seroconversion rate and the seroprotection rate exceeded 2.5, 40% and 70% for the four strains in IIV4-W respectively. CONCLUSIONS: IIV4-W was noninferior to the TIV-matched strains and was superior to the additional B strain. IIV4-W was safe in the participants and elicited high antibody titers.

Immunogenicity of influenza vaccine in elderly people: a systematic review and meta-analysis of randomized controlled trials, and its association with real-world effectiveness.

Background: Older people (≥60 years old) are particularly vulnerable to influenza virus infection, and vaccine is effective in reducing the disease burden in this population. However, it remains obscure whether their antibody response is lower than those of younger adults (18-60 years old). Thus, this meta-analysis was performed to compare the immunogenicity of influenza vaccines and understand their association with real-world vaccine effectiveness (VE) between these two age groups. Methods: A systematic literature search was conducted to identify relevant studies from Jan 01, 2008 to Nov 10, 2018. These are randomized controlled trials that included older adult samples, which assessed the immunogenicity of inactivated quadrivalent influenza vaccines produced in embryonated eggs. We excluded the studies focused only in children or adults. The outcomes were seroprotecton rate (SPR) and seroconversion rate (SCR). Results: Six studies were eventually included in the present meta-analysis (7,976 participants). For the SPR, the pooled risk ratio (RR) was 0.92 (95% CI: 0.90-0.94, I2 = 66%, P < .0001) for A/H1N1 and 0.94 (95% CI: 0.90-0.98, I2 = 91%, P = .002) for B/Victoria, and the antibody responses of A/H3N2 and B/Yamagata were similar in the two age groups. For the SCR, the pooled RR was 0.85 (95% CI: 0.76-0.94, I2 = 93%, P = .003), 0.77 (95% CI: 0.66-0.91, I2 = 94%, P = .002), and 0.83 (95% CI: 0.71-0.96, I2 = 94%, P = .02) for A/H1N1, B/Victoria and B/Yamagata, respectively, and the antibody responses of A/H3N2 were similar in the two groups. Some variations were found in the antibody responses across virus types and subtypes after influenza vaccination. Conclusion: The SPR and SCR of older adults were lower than those in younger adults for A/H1N1 and B/Victoria, while the two age groups had similar antibody responses for A/H3N2. The antibody responses to vaccines were not significantly associated with real-world VE, indicating that antibody response might not fully reflect the vaccine effectiveness of A/H3N2.

Development of a relative potency test using ELISA for human rabies vaccines.

The NIH potency test for human rabies vaccines has disadvantages for use, especially in developing countries where rabies is endemic and prophylaxis needs ample, rapid, and reliable vaccine supplies. In China, 60-75 million doses of human rabies vaccines are administered each year. Vaccine quality control is of paramount importance, as is the release of potency-validated vaccines. We intended to design an alternative to the NIH in vivo method, and developed a relative potency test using an ELISA. Using Pearson's correlation analysis, we found a close relationship between the rabies vaccine glycoprotein content in vitro and the potency values in vivo. We suggest the relative potency test developed here as a simplified method for human rabies vaccine quality control in China and a possible alternative to the NIH method.

The complete mitochondrial genome of Pseudogyrinocheilus prochilus (Cypriniformes: Cyprinidae).

The complete mitochondrial sequence of Pseudogyrinocheilus prochilus, an endemic species to China and mainly distributed in upper Yangtze River and its tributaries, was obtained by PCR. It was 16,595 bp in length and comprised 37 mitochondrial genes (22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal RNA genes) and 2 non-coding regions. The overall base composition of H-strand was 31.40% A, 26.78% C, 16.18% G, and 25.64% T. Most of the genes are encoded on heavy strand, except for eight tRNA and ND6 genes. The composition and order of mitochondrial gene have no unique characteristics compared to most of other fishes.

The complete mitochondrial genome sequence of Schizothorax dolichonema (Cypriniformes: Cyprinidae).

The complete mitochondrial genome sequence of Schizothorax dolichonema has been sequenced, which contains 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes and 2 non-coding regions: origin of light-strand replication and control region, with the total length of 16,583 bp. The gene order and composition are similar to most of other vertebrates. Most of the genes are encoded on heavy strand, except for eight tRNA and ND6 genes. The mitogenome sequence of S. dolichonema would contribute for better understanding of biogeography and evolution of Schizothoracine fishes.

The complete mitochondrial genome sequence of Schizothorax lissolabiatus (Cypriniformes: Cyprinidae).

Schizothorax lissolabiatus is a widely distributed fish species in Lancang River, Yuanjiang River, Pearl River, Nujiang River in China. The complete mitochondrial genome sequence of S. lissolabiatus from Yuanjiang River (the upper Red River) has been sequenced, which is 16,583 bp in length and contains 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes and 2 main non-coding regions: origin of light-strand replication and control region. Except for eight tRNA and ND6 genes, most of the genes are encoded on the heavy strand. The length of mitochondrial genome, the order, composition and anticodons of all genes are exactly similar to that of S. dolichonema. The phylogenetic tree suggested S. prenanti, S. dolichonema and S. lissolabiatus may have closer affinities than other fish of the genus Schizothorax.