A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing ...the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 46%), fatigue (47 44%), headache (42 39%), and muscle pain (18 17%. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel ...controlled trial to evaluate the safety and immunogenicity of the bivalent (5×10
viral particles) and B.1.1.529 variant (5×10
viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×10
viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.
Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety ...and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster.
This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 10
viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 10
viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing.
Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 48·0-71·4; p<0·0001).
A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac.
National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.
Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and ...immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac).
We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing.
Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 12% of 110 children and 22 20% of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 51% of 35 children and 17 49% of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five 14% of 35 children and eight 23% of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 12% of 110 children and 21 10% of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 49% of 35 children and 17 49% of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five 14% of 35 children and seven 20% of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 95% CI 8·0-13·1; p<0·0001).
Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents.
National Key R&D Program of China.
A specific gas chromatographic (GC) detection method for edible bird’s nest (EBN) based on identifying the composition of the oligosaccharide chain combined with glycoprotein in EBN is developed. ...Five monoses (D-mannitose, D-galactose, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, and N-acetyl neuraminate) that constitute the oligosaccharide chain are detected using GC and GC—mass spectrometry techniques; their characteristic GC spectrum can reliably be regarded as EBN’s fingerprint. The peak-area ratios in GC spectrum of those five monoses are found to be fixed; therefore, the GC technique developed in this work can conveniently be used to determine various raw EBNs and their products both qualitatively and quantitatively, distinguishing between fake and genuine EBN rapidly.
Malignant gliomas are aggressive primary neoplasms that originate in the glial cells of the brain or the spine with notable resistance to standard treatment options. We carried out the study with the ...aim to shed light on the sensitization of resveratrol to temozolomide (TMZ) against glioma through the Wnt signaling pathway. Initially, glioma cell lines with strong resistance to TMZ were selected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Then, the glioma cells were subjected to resveratrol, TMZ, Wnt signaling pathway inhibitors, and activators. Cell survival rate and inhibitory concentration at half maximum value were detected by MTT, apoptosis by flow cytometry, and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining, in vitro proliferation by hanging drop method and β‐catenin translocation into nuclei by TOP/FOP‐FLASH assay. The expressions of the Wnt signaling pathway‐related and apoptosis‐related factors were determined by western blot analysis. Nude mice with glioma xenograft were established to detect tumorigenic ability. Glioma cell lines T98G and U138 which were highly resistant to TMZ were selected for subsequent experiments. Resveratrol increased the efficacy of TMZ by restraining cell proliferation, tumor growth, and promoting cell apoptosis in glioma cells. Resveratrol inhibited Wnt2 and β‐catenin expressions yet elevated GSK‐3β expression. Moreover, the Wnt signaling pathway participates in the sensitivity enhancing of resveratrol to TMZ via regulating
O
6‐methylguanine‐DNA methyltransferase (MGMT) expression. Resveratrol sensitized TMZ‐induced glioma cell apoptosis by repressing the activation of the Wnt signaling pathway and downregulating MGMT expression, which may confer new thoughts to the chemotherapy of glioma.
Resveratrol sensitized temozolomide (TMZ)‐induced glioma cell apoptosis by repressing the activation of the Wnt signaling pathway and downregulating O
6‐methylguanine‐DNA methyltransferase (MGMT) expression, which may confer new thoughts to the chemotherapy of glioma.
Coloring in apple fruit due to anthocyanin accumulation is inhibited by high temperature; however, the underlying mechanism remains unclear. In the present study, total anthocyanin and cyanidin ...3-galactoside contents were determined and compared between cv. 'Redchief Delicious' apple fruits at 25 °C and 35 °C treatments. The high temperature (35 °C) treatment substantially decreased total anthocyanin and cyanidin 3-galactoside contents. The transcriptomes of 25 °C- and 35 °C-treated apples were analyzed by high-throughput RNA sequencing. A total of 8354 differentially expressed genes (DEGs) were detected at four time points corresponding to the two temperature treatments. The up-regulated DEGs were annotated using GO as well as KEGG databases. A network module of 528 genes (including 21 transcription factors) most associated with the total anthocyanin and cyanidin 3-galactoside contents was constructed by weighted correlation network analysis (WGCNA). In the WGCNA module, we unearthed a LOB domain-containing gene designated as
. The expression of
was sharply up-regulated by high temperature and negatively correlated with the total anthocyanin and cyanidin 3-galactoside contents. Overexpression of
in apple fruit and calli decreased the expression of anthocyanin biosynthetic genes, such as
,
,
,
,
, and
, along with anthocyanin accumulation. Our results suggested that
significantly influenced the high-temperature inhibition of anthocyanin accumulation in apples. The findings shed more light on the mechanism of anthocyanin inhibition during high-temperature stress in apples.
The intestinal biota, known for its colonization of the human intestine and its modulation of host pathophysiological responses through the immune and endocrine systems, has gained substantial ...interest in recent years due to its notable correlation with diabetes and stroke.
In order to examine this association, a comparative study was conducted on the intestinal biota and blood samples obtained from mouse models and type 2 diabetic patients with and without stroke complications. Advanced techniques, such as high-throughput sequencing and enzyme-linked immunosorbent assay were employed to identify the differences in the intestinal biota and blood indices of mouse models and patients.
At the phylum level, the dominant gut bacteria identified in patients with diabetes mellitus and stroke were Firmicutes, Bacteroidetes, and Proteobacteria. It was noteworthy that the relative abundance of Bacteroides at the genus level was significantly diminished in the DB-PT group (photothrombotic diabetes mice) as compared to the DB group (diabetesmice). This result was consistent with observations in human samples. Additionally, significant variations were detected in lipid proteins, specifically APOA4, in diabetic patients with and without stroke.
Stroke can diminish the abundance and diversity of intestinal biota, potentially correlating with lipid proteins in patients with diabetes.
Riptortus pedestris is one of the most destructive pests of leguminous crops in East Asia. In this study, we assessed the effect of different leguminous plant species, including soybean, wild ...soybean, white kidney bean, runner bean, pea, cowpea, adzuki bean, mung bean, faba bean, and lentil vetch, on the development and reproduction of R. pedestris. We found that leguminous plant species significantly affect the developmental duration and survivability of the nymphs, adult longevity, and oviposition and fecundity in R. pedestris. The nymphs completed their development on all of these plants. The developmental duration of nymphs was the shortest (16.24 ± 0.57 days) on soybean and the longest (31.33 ± 1.76 days) on faba bean. The rates of survival of nymphs on soybean and pea were 93.2% and 93.0%, respectively. Female adults survived the longest on soybean (64.67 ± 6.64 days) and the shortest (13.27 ± 3.67 days) on white kidney bean. The fecundity on faba bean (decorticated pods) (143.0 ± 28.04 eggs) and soybean (116.63 ± 12.76 eggs) was higher than those on other plants. The age‐specific life table revealed that the population trend index values were all >1 except on wild soybean and faba bean, and the highest was on soybean (30.36), followed by pea (21.0). Soybean and pea were identified as the most suitable hosts for R. pedestris because of their shorter developmental duration, higher survivability, longevity and fecundity and greater population trend index on these hosts, while wild soybean and faba bean were relatively unsuitable host plants.
The bean bug, Riptortus pedestris, is a polyphagous pest distributed in Asian countries. This study provides fundamental findings on the effect of leguminous pods on the development, survival, fecundity and population growth of R. pedestris. Legumes, especially soybean, are the ideal food sources of R. pedestris, except wild soybean and faba bean. The findings of this study will assist in predicting the occurrence, population dynamics and control tactics of this pest.
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