Publications by authors named "Jing-Xin Li"

59 Publications

Safety and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older: two single-center, randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials.

Signal Transduct Target Ther 2021 07 15;6(1):271. Epub 2021 Jul 15.

NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.
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http://dx.doi.org/10.1038/s41392-021-00692-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281021PMC
July 2021

Next steps for efficacy evaluation in clinical trials of COVID-19 vaccines.

Engineering (Beijing) 2021 May 19. Epub 2021 May 19.

School of Public Health, Southeast University, Nanjing 210009, China.

There are currently ten COVID-19 vaccines being announced their preliminary efficacies from phase 3 clinical trial, and nine of them have been authorized for emergency use or conditional licensed, which brings some issues to present placebocontrolled efficacy trial of other COVID-19 vaccines. The approval of "first wave" COVID-19 vaccines raises concerns about the administration of a placebo in ongoing and future phase 3 trials of COVID-19 vaccine candidates. Comprehensive efficacy assessment strategy for the next steps is now required. This perspective covers challenges for ongoing COVID-19 vaccine clinical studies and alternative clinical study designs in the future, under the placebo use being acceptable or unacceptable circumstances, respectively, in order to ensure the safety, efficacy and effectiveness evaluation of COVID-19 candidate vaccines pre- and post-licensure.
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http://dx.doi.org/10.1016/j.eng.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186691PMC
May 2021

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.

Chin Med J (Engl) 2021 Apr 28;134(11):1289-1298. Epub 2021 Apr 28.

NHC Key Laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention), Nanjing, Jiangsu 210009, China.

Background: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.

Methods: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.

Results: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.

Conclusions: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.

Trial Registration: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
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http://dx.doi.org/10.1097/CM9.0000000000001573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183795PMC
April 2021

Amentoflavone from Selaginella tamariscina as a potent inhibitor of gut bacterial β-glucuronidase: Inhibition kinetics and molecular dynamics stimulation.

Chem Biol Interact 2021 May 27;340:109453. Epub 2021 Mar 27.

Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address:

Gut bacterial β-glucuronidase (GUS) plays a pivotal role in the metabolism and reactivation of a vast of glucuronide conjugates of both endogenous and xenobiotic compounds in the gastrointestinal tract of human, which has been implicated in certain drug-induced gastrointestinal tract (GI) toxicity in clinic. Inhibitors of gut microbial GUS exhibited great potentials in relieving the drug-induced GI toxicity. In this study, Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) were evaluated for their inhibitory activity against Escherichia coli GUS. Two selective probe substrates for GUS (a specific fluorescent probe substrate for GUS, DDAOG and a classical drug substrate for GUS, SN38G) were used in parallel for charactering the inhibition behaviors. Both the extract of S. tamariscina and its major biflavonoid AMF displayed evident inhibitory effects on GUS, and the IC values of AMF against GUS mediated DDAOG and SN-38G hydrolysis were 0.62 and 0.49 μM, respectively. Inhibition kinetics studies indicated that AMF showed mixed type inhibition for GUS-mediated DDAOG hydrolysis, while displayed competitive type inhibition against GUS-mediated SN-38G hydrolysis, with the K values of 0.24 and 1.25 μM, respectively. Molecular docking studies and molecular dynamics stimulation results clarified the role of amino acid residues Leu361, Ile363, and Glu413 in the inhibition of AMF on GUS. These results provided some foundations for the potential clinical utility of S. tamariscina and its major biflavonoid AMF for treating drug-induced enteropathy.
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http://dx.doi.org/10.1016/j.cbi.2021.109453DOI Listing
May 2021

Adjuvantation helps to optimise COVID-19 vaccine candidate.

Lancet Infect Dis 2021 07 8;21(7):891-893. Epub 2021 Mar 8.

NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00094-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221731PMC
July 2021

Quadrivalent influenza vaccine (Sinovac Biotech) for seasonal influenza prophylaxis.

Expert Rev Vaccines 2021 Jan 1;20(1):1-11. Epub 2021 Feb 1.

School of Public Health, Southeast University; Nanjing, China.

Introduction: Quadrivalent Influenza Vaccine (Sinovac Biotech) is a quadrivalent split-virion-inactivated influenza vaccine approved in China in June 2020 for individuals ≥3 years of age. It contains 15 µg hemagglutinin per strain including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, which could potentially improve protection against influenza B viruses.

Areas Covered: In this review, we summarize the development of quadrivalent influenza vaccines in China and foreign countries, and assess the immunogenicity and safety from the phase I and III clinical trials of Quadrivalent Influenza Vaccine in individuals ≥3 years of age. We also discuss the potential application of Quadrivalent Influenza Vaccine in young children 6-35 months of age according to the results of the phase III trial.

Expert Commentary: The immunogenicity and safety profiles of Quadrivalent Influenza Vaccine containing two A and two B strains were comparable to the trivalent vaccines for the shared strains. The addition of a second B strain to the trivalent vaccine could induce superior immune responses for the alternate B strain. Since the two B strains co-circulated worldwide, the introduction of quadrivalent influenza vaccines has been expected to be a cost-effective strategy.
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http://dx.doi.org/10.1080/14760584.2021.1875823DOI Listing
January 2021

Novel insight from the first lung transplant of a COVID-19 patient.

Eur J Clin Invest 2021 Jan 20;51(1):e13443. Epub 2020 Nov 20.

Department of Forensic Medicine, Nanjing Medical University, Nanjing, China.

Background: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient.

Materials And Methods: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis.

Results: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3 CD4 T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1β and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation.

Conclusions: Our results provide novel insight that the significant neutrophil/ CD3 CD4 T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.
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http://dx.doi.org/10.1111/eci.13443DOI Listing
January 2021

Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine.

Open Forum Infect Dis 2020 Aug 26;7(8):ofaa181. Epub 2020 May 26.

School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Background: In this study, we investigated the effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants.

Method: We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples were collected and tested by hemagglutination-inhibition tests during the 2015-2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated.

Results: Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (  = .038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming (  = .036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming ( = .012). Antigenic distance was well matched with serological results. Moeover, age-specific differences in human postvaccination responses against the identical circulating strain was noted. In addition, children had the most cross-reactive response to both H3N2 and B-yamagata subtypes.

Conclusions: Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific postvaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human postvaccination responses.
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http://dx.doi.org/10.1093/ofid/ofaa181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423295PMC
August 2020

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet 2020 08 20;396(10249):479-488. Epub 2020 Jul 20.

Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China. Electronic address:

Background: 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.

Methods: 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 × 10 viral particles per mL or 5 × 10 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.

Findings: 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 × 10 viral particles n=253; 5 × 10 viral particles n=129) or placebo (n=126). In the 1 × 10 and 5 × 10 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 × 10 and 5 × 10 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 × 10 and 5 × 10 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 10 and 5 × 10 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 10 viral particles dose group and one (1%) participant in the 5 × 10 viral particles dose group. No serious adverse reactions were documented.

Interpretation: The Ad5-vectored COVID-19 vaccine at 5 × 10 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.

Funding: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
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http://dx.doi.org/10.1016/S0140-6736(20)31605-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836858PMC
August 2020

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.

Lancet 2020 06 22;395(10240):1845-1854. Epub 2020 May 22.

Beijing Institute of Biotechnology, Beijing, China. Electronic address:

Background: 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.

Methods: 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 × 10, 1 × 10, and 1·5 × 10 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.

Findings: 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.

Interpretation: 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.

Funding: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
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http://dx.doi.org/10.1016/S0140-6736(20)31208-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255193PMC
June 2020

High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats.

Chin Med J (Engl) 2020 May;133(10):1182-1191

Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

Background: Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.

Methods: The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively.

Results: The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = -10.213, P < 0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all P > 0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t = -21.915, P < 0.001) and expression of renal ANP (t = -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t = 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t = -4.685, P = 0.009), lipofuscin (t = -8.195, P = 0.001), and Nox (t = -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05).

Conclusions: The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.
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http://dx.doi.org/10.1097/CM9.0000000000000752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249711PMC
May 2020

The vaccines-associated Arthus reaction.

Hum Vaccin Immunother 2019 3;15(11):2769-2777. Epub 2019 May 3.

Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu, China.

The Arthus reaction is a rare adverse reaction that usually occurs after vaccination with large and more severe local reactions, belonging to type Ⅲ hypersensitivity reaction. This reaction is characterized by pain, swelling, induration (Tissue that becomes firm) and edema, even accompanied by severe necrosis or ulceration at the injection sites. However, most of mild cases generally can be cured without treatment, and only severe cases need to be treated with anti-allergy. Therefore, this adverse reaction is often ignored by people.We searched PubMed, Web of Science and Chinese database (CNKI database and Wan Fang database) for published studies using the terms "Arthus reaction" or "Arthus phenomenon", combined with "vaccine", with no date or language restrictions for all publications before January 28, 2019. Only 30 cases of Arthus reaction were found, of which only one case died.4 cases of Arthus reaction post-dose-1 were reported in the review. The proportion of Arthus reaction occurred after the first, second and third injections in those case reports was 13.3%, 50.0%, and 23.3%, respectively. Arthus reaction was determined according to the clinical symptoms (The symptoms which were observed by the researchers, such as red, swelling and painful with itching at or around the injection sites). The specific causes of Arthus reaction after one dose of vaccination are not described in detail in literatures. Therefore, it could be hypothesized that the case has a pre-existing specific IgG (Such as pre-existing antibody, etc.) to cause the Arthus reaction.And 17 reported cases were observed in children younger than 6 y. In addition, we collected only 18 cases of bacterial vaccine-induced Arthus reaction and 12 cases of viral vaccines. However, there are no other data (Such as the total number and incidence rate of vaccination) in literatures, so we cannot compare statistically significant differences. At presents, no previous reviews of vaccine-induced Arthus reaction have been found. Thus, a systematic review about vaccine-associated Arthus reaction is urgently needed to deepen people's understanding and concern of this phenomenon. In this manuscript, we retrospectively reviewed the description of the discovery process and mechanisms of Arthus reaction, a description of the characteristics of Arthus reaction cases, reporting the Arthus reaction cases in China during 2010-2015, diagnostic criteria and general treatment, preventive measures of Arthus reaction, and challenges remaining to be investigated in the future.
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http://dx.doi.org/10.1080/21645515.2019.1602435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930064PMC
May 2020

Vasopressin augments TNBS-induced colitis through enteric neuronal V receptor-mediated COX-2-dependent prostaglandin release from mast cells in mice.

Neurogastroenterol Motil 2019 02 18;31(2):e13493. Epub 2018 Oct 18.

Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Background: Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway.

Methods: Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg )-Vasopressin (AVP)-evoked short-circuit current (Isc) was recorded in the presence of conivaptan (V and V receptor antagonist), tolvaptan (V receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX-1 antagonist; NS560, COX-2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively.

Key Results: TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS-induced colitis, which was attenuated by conivaptan but not tolvaptan. V receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8-15 µA/cm , 10-11 mHz, and 1.5 minutes, respectively. Notably, the AVP-evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively.

Conclusions And Inferences: VP-V receptor played the proinflammatory role in TNBS-induced colitis by promoting COX-2-dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.
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http://dx.doi.org/10.1111/nmo.13493DOI Listing
February 2019

[Quantitative assessment of urban ecosystem services flow based on entropy theory: A case study of Beijing, China].

Ying Yong Sheng Tai Xue Bao 2018 Mar;29(3):987-996

School of Nature Conservation, Beijing Forestry University, Beijing 100083, China.

Quantitative evaluation of ecosystem service is a primary premise for rational resources exploitation and sustainable development. Examining ecosystem services flow provides a scientific method to quantity ecosystem services. We built an assessment indicator system based on land cover/land use under the framework of four types of ecosystem services. The types of ecosystem services flow were reclassified. Using entropy theory, disorder degree and developing trend of indicators and urban ecosystem were quantitatively assessed. Beijing was chosen as the study area, and twenty-four indicators were selected for evaluation. The results showed that the entropy value of Beijing urban ecosystem during 2004 to 2015 was 0.794 and the entropy flow was -0.024, suggesting a large disordered degree and near verge of non-health. The system got maximum values for three times, while the mean annual variation of the system entropy value increased gradually in three periods, indicating that human activities had negative effects on urban ecosystem. Entropy flow reached minimum value in 2007, implying the environmental quality was the best in 2007. The determination coefficient for the fitting function of total permanent population in Beijing and urban ecosystem entropy flow was 0.921, indicating that urban ecosystem health was highly correlated with total permanent population.
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http://dx.doi.org/10.13287/j.1001-9332.201803.017DOI Listing
March 2018

Seroepidemiology of enterovirus D68 infection in infants and children in Jiangsu, China.

J Infect 2018 06 8;76(6):563-569. Epub 2018 Feb 8.

National Institutes for Food and Drug Control, Beijing, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2018.02.003DOI Listing
June 2018

A comparative analysis of immunogenicity and safety of an enterovirus 71 vaccine between children aged 3-5 years and infants aged 6-35 months.

Expert Rev Vaccines 2018 03 29;17(3):257-262. Epub 2018 Jan 29.

a School of Public Health , Nanjing Medical University , Nanjing , PR China.

Background: The Sinovac enterovirus 71 (EV71) vaccine has shown good safety, immunogenicity, and efficacy in infants aged 6-35 months, whom are considered as the priority of the target population. However, 3-5 years old children accounted for approximately 30% of HFMD cases and are also worth our attention.

Methods: A randomized, double-blind, placebo-controlled, batch-to-batch consistency clinical trial enrolling 1400 participants aged 6-59 months was performed. We pooled the participants receiving three batches of EV71 vaccine together and then stratified them into the 6-35 months and 3-5 years. The non-inferiority analysis of the geometric mean titer (GMT) of EV71 neutralizing antibody post-vaccination was the primary endpoint.

Results: In the vaccine group, the GMT of 242 children aged 3-5 years was 132.72 (95% CI, 110.3-159.6), which was non-inferior to that generated in 717 infants aged 6-35 months. Following the vaccination, the incidence of adverse reactions was less frequent in children aged 3-5 years (47.0%) than that found in infants aged 6-35 months (60.1%) (p = 0.0026).

Conclusions: Our study indicated that the EV71 vaccine was also safe in children aged 3-5 years, with non-inferior immunogenicity to that in infants aged 6-35 months.
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http://dx.doi.org/10.1080/14760584.2018.1430572DOI Listing
March 2018

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccines in participants >/=3 years of age: a double-blind, randomized, parallel-controlled phase III clinical trial in China.

Expert Rev Vaccines 2017 11 18;16(11):1155-1169. Epub 2017 Sep 18.

d Corporate Representative , Jiangsu GDK Biotechnology Co., Ltd , Taizhou , PR China.

Background: Viruses from two antigenically distinct influenza B strains have co-circulated since the mid-1980s, yet inactivated trivalent influenza vaccines (TIVs) with either the Victoria or Yamagata lineage could only provide limited protection from influenza B strain. Quadrivalent influenza vaccine (QIV) including both influenza B lineages can improve protection against circulating influenza B viruses.

Methods: Participants >/ = 3 years of age were recruited, stratified by age, and then randomly allocated at a ratio of 2:1:1 to receive one-injection of the experimental QIV, TIV-Victoria (Vic) or TIV-Yamagata (Yam). The primary objective of this study was to demonstrate that the hemagglutination-inhibition (HI) antibodies induced by the QIV candidate are not inferior to the licensed TIVs.

Results: First, 3661 participants received the inoculation. The QIV was found to be non-inferior to TIVs in terms of the geometric mean titers (GMTs) and seroconversion rates (SCRs) of the HI antibodies against shared strains 28 days after completion of inoculation, and was superior to the TIVs against the alternate B strain, which is absent from the TIVs. The occurrences of adverse events (AEs) post-vaccination were similar across the treatment groups.

Conclusion: The experimental QIV showed good immunogenicity and an acceptable safety profile.
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http://dx.doi.org/10.1080/14760584.2017.1374181DOI Listing
November 2017

Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

Expert Rev Vaccines 2017 09 12;16(9):945-949. Epub 2017 Jun 12.

a Department of Public Health , Southeast University , Nanjing , China.

Background: Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors.

Methods: Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively.

Results: For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months.

Conclusion: Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection.

Clinical Trial Registration: NCT01508247.
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http://dx.doi.org/10.1080/14760584.2017.1335603DOI Listing
September 2017

The immunogenicity and safety of a Hib-MenAC vaccine: a non-inferiority randomized, observer-blind trial in infants aged 3-5 months.

Expert Rev Vaccines 2017 May 31;16(5):515-524. Epub 2017 Mar 31.

a School of Public Health , Southeast University , Nanjing , PR China.

Background: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup A and C-tetanus toxoid conjugate vaccine (Hib-MenAC).

Methods: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3-5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint.

Results: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination.

Conclusions: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months.
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http://dx.doi.org/10.1080/14760584.2017.1303380DOI Listing
May 2017

Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.

Lancet Glob Health 2017 03 23;5(3):e324-e334. Epub 2016 Dec 23.

Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China. Electronic address:

Background: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China.

Methods: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 10 viral particles, 1·6 × 10 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively.

Findings: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 10 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 10 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group.

Interpretation: The adenovirus 5-vectored Ebola vaccine of 1·6 × 10 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 10 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease.

Funding: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
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http://dx.doi.org/10.1016/S2214-109X(16)30367-9DOI Listing
March 2017

Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet 2017 02 23;389(10069):621-628. Epub 2016 Dec 23.

Beijing Institute of Biotechnology, Beijing, China. Electronic address:

Background: A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose.

Methods: We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18-50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 10 viral particles), low-dose vaccine (8·0 × 10 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed.

Findings: During Oct 10-28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 [95% CI 976·6-1602·5] in low-dose group and 1728·4 [1459·4-2047·0] in high-dose group) and peaked at day 28 (1471·8 [1151·0-1881·8] and 2043·1 [1762·4-2368·4]), but declined quickly in the following months (223·3 [148·2-336·4] and 254·2 [185·0-349·5] at day 168). Geometric mean titres in the placebo group remained around 6·0-6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine.

Interpretation: The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 10 viral particles was the optimal dose.

Funding: Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
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http://dx.doi.org/10.1016/S0140-6736(16)32617-4DOI Listing
February 2017

Epidemiological and etiological characteristics of herpangina and hand foot mouth diseases in Jiangsu, China, 2013-2014.

Hum Vaccin Immunother 2017 04 21;13(4):823-830. Epub 2016 Oct 21.

a National Institute for Food and Drug Control , Beijing , China.

Herpangina (HA) and hand, foot, and mouth disease (HFMD) are common infectious diseases caused by human enteroviruses and frequently occurr in young children. Previous published studies have mainly focused on HFMD, while the HA epidemiological and etiological characteristics in mainland China have not been described. From June, 2013 to March, 2014, HA and HFMD patients were monitored in participants from clinical trial of EV-A71 vaccine conducted during 2012-2013. A total of 95 HA patients and 161 HFMD patients were defined. Enteroviruses of HA samples were differentiated into 17 serotypes (EV-A71, CV-A16, CV-A24, E6, CV-B5, CV-A22, CV-A6, CV-A10, CV-B3, E9, CV-A9, CV-B4, CV-B2, E1, E7, E21 and CV-A20), the most common serotypes were EV-A71(10/95,10.5%), CV-A16(4/95,4.2%) and CV-A24(4/95,4.2%); while enteroviruses detected from HFMD samples were classfied into 21 serotypes ( EV-A71, CV-A16, CV-A10, CV-A6, E6, CV-B3, CV-B5, CV-A9, E9, CV-B2, CV-B4, E3, E11, E15, E16, CV-A1, EV-A69, E5, CA22, CA24 and EV99), the most common serotypes were EV-A71(28/161,17.4%), CV-A16(7/161,4.4%) and CV-A10(5/161,3.1%). The first HA epidemic peak occurred in summer and a second smaller peak occurred in January. In HA patients, the body temperature (P < 0.0001) and the incidence of fever (P < 0.05) were significant higher than those in HFMD patients. Between HA and HFMD patients infected with EV-A71, no significant differences were found in age, sex, circulating season, and the viral genome diversity. In summary, we firstly reported the epidemiological and etiological characteristics of HA in mainland China. Developing a multivalent vaccine will be helpful for the control of the HA/HFMD epidemic.
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http://dx.doi.org/10.1080/21645515.2016.1236879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404359PMC
April 2017

Norovirus Infection and Histo-blood Group Antigens in Children Hospitalized with Diarrhea in Lulong and Chenzhou in China.

Biomed Environ Sci 2016 04;29(4):286-9

Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing 102206, China; National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.

Norovirus (NoV) is a pathogen that commonly causes viral diarrhea in children. Studies indicate that NoV recognizes human histo-blood group antigens (HBGAs) as cell attachment factors. In order to explore the correlation between of NoV infection and HBGAs, a cross-sectional study was conducted in children less than five years old who were hospitalized with diarrhea in two areas of China between November 2014 and February 2015. Of the paired stool and saliva samples taken from 424 children, NoV was detected in 24 (6%) children, with viral genotypes GII.3 (n=5), GII.4 (n=14), GII.12 (n=1), and GII.17 (n=4). All of the individuals having NoV infection were either secretors (Lea-b+/Lex-y+) or partial secretors (Lea+b+/Lex+y+) except one GII.3 infection of a non-secretor (Lea+b-/Lex+y-). These results suggest that secretor positive is associated with NoV infection, although non-secretors are not absolutely protected from NoV infection.
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http://dx.doi.org/10.3967/bes2016.036DOI Listing
April 2016

Enterovirus 71: a whole virion inactivated enterovirus 71 vaccine.

Expert Rev Vaccines 2016 07 6;15(7):803-13. Epub 2016 Jun 6.

b Department of Vaccine Clinical Evaluation , Jiangsu Provincial Center for Disease Control and Prevention , Nanjing , PR China.

Introduction: Enterovirus A71 (EV71) is the predominant causative agent of hand, foot, and mouth disease (HFMD), which is often associated with severe cases and even deaths. EV71-associated epidemics have emerged as a serious threat to public health, particularly in the Asia-Pacific region.

Areas Covered: We searched PubMed using the terms 'enterovirus 71', 'hand, foot, and mouth disease', and 'vaccine', with no date or language restrictions for all publications before April 27, 2016. Among various vaccine candidates, the alum-adjuvant inactivated EV71 vaccines are most promising. Three alum-adjuvant inactivated EV71 vaccines developed by mainland China showed high efficacy, good immunogenicity persistence and acceptable safety profiles in clinical trials. Recently, two of these EV71 vaccines have been approved for marketing in China and the other one is undergoing the review process of licensure. In this manuscript, we summarized previous study results as well as discussed the regulatory affairs and post-market surveillances issues. Expert commentary: The marketing of EV71 vaccines is a milestone in the controlling of HFMD. International clinical trials are needed to further assess the efficacy and cross-immunogenicity. Establishing a sensitive pathogen monitoring system would be essential to monitor the variation of genotypes and control HFMD epidemics.
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http://dx.doi.org/10.1080/14760584.2016.1191357DOI Listing
July 2016

An epidemic of coxsackievirus B3 infection in infants and children in Jiangsu Province, China: a prospective cohort study.

Arch Virol 2016 Jul 28;161(7):1945-7. Epub 2016 Mar 28.

National Institutes for Food and Drug Control, No. 2, Tiantan Xili, Beijing, 100050, People's Republic of China.

To investigate the epidemiological data on coxsackievirus B3 (CVB3) infection and its incidence in infants and children, a prospective cohort study was carried out from 2012 to 2014 in Jiangsu Province, China. According to the results of seropositive rates and NTAb titers of CVB3, an epidemic of CVB3 infection was found, and a dynamic change in CVB3 neutralizing antibody was also observed. One case was recorded with CVB3-associated hand, foot and mouth disease (HFMD), and the isolates belonged to the CVB3 D2 subtype. Our data help us to better understand the epidemic characteristics of CVB3 infection in infants and children.
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http://dx.doi.org/10.1007/s00705-016-2842-7DOI Listing
July 2016

Helicobacter pylori vaccination - Authors' reply.

Lancet 2016 Feb 18;387(10020):749. Epub 2016 Feb 18.

Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(16)00008-8DOI Listing
February 2016

Two-year efficacy and immunogenicity of Sinovac Enterovirus 71 vaccine against hand, foot and mouth disease in children.

Expert Rev Vaccines 2016 13;15(1):129-37. Epub 2015 Oct 13.

b Vaccine Clinical Evaluation Department , Jiangsu Provincial Center for Disease Control and Prevention , Nanjing , PR China.

Objectives: To evaluate the efficacy and immunogenicity of the Sinovac Enterovirus 71 (EV71) vaccine for up to two years.

Methods: We did a follow-up study of our initial randomized trial in 10,077 participants, who were randomized to receive EV71 vaccine or placebo in a 1:1 ratio and followed for 14 months. The extended follow-up study lasted for another 12 months and EV71-associated hand, foot, and mouth disease (HFMD) was the primary endpoint.

Results: The EV71 vaccine showed an efficacy of 95.1% (95%CI 63.6, 99.3) against EV71-associated HFMD during the extended follow-up and an overall efficacy of 94.7% (95%CI 87.8, 97.6) for two years. The EV71 vaccine elicited a sustained high level of neutralizing antibodies in participants, and no serious adverse event was judged to be related to the vaccination.

Conclusion: The Sinovac EV71 vaccine could provide a sustained high protection against EV71-associated HFMDs for up to 2 years.
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http://dx.doi.org/10.1586/14760584.2016.1096782DOI Listing
September 2016

Disease burden of enterovirus 71 in rural central China: A community-based survey.

Hum Vaccin Immunother 2015 ;11(10):2400-5

b Jiangsu Provincial Center for Disease Control and Prevention ; Nanjing , Jiangsu Province , PR China.

In recent years, the epidemics of hand, foot, and mouth disease (HFMD) centered in the Asian-Pacific region have been characterized by high morbidity and mortality. Enterovirus 71 (EV71) infections were responsible for the majority of the infections leading to severe cases of HFMD and death. This is a community-based survey aimed to estimate the disease burden of EV71 in rural central China, especially for HFMD. From 2011 to 2013, demographic and socio-economic data were gathered from 343 ill children and their parents using a structured questionnaire. We quantified the health burden of disease resulting from EV71 infection in disability-adjusted life years (DALYs). Among 343 cases, 303 had confirmed HFMD, 6 presented with herpangina, 25 presented with respiratory symptoms, and 9 presented with non-specific symptoms. The number of severe cases was 47 (including 1 death) and all of these presented with HFMD. The total cost per patient for severe HFMD, mild HFMD, herpangina, respiratory disease, and non-specific disease was $2149.47, $513.22, $53.28, $31.95, and $39.25, respectively. The overall cost of EV71-related diseases as a proportion of local farmers' per capita net income ranged from 0.18% for those with non-specific disease to 187.12% for those with severe HFMD. The loss of DALYs for the 5 forms of disease were 3.47, 1.76, 1.07, 1.44, 1.22 person-years per 1000 persons, respectively. This study provides data on cost of treatment and health burden for diseases caused by EV71, which can be used in the evaluation of EV71 vaccine cost-effectiveness.
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http://dx.doi.org/10.1080/21645515.2015.1059980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635911PMC
June 2016

Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet 2015 Oct 30;386(10002):1457-64. Epub 2015 Jun 30.

College of Pharmacy, Third Military Medical University, Chongqing, China. Electronic address:

Background: Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China.

Methods: We did this randomised, double-blind, placebo-controlled, phase 3 trial at one centre in Ganyu County, Jiangsu Province, China. Healthy children aged 6-15 years without past or present H pylori infection were randomly assigned (1:1), via computer-generated randomisation codes in blocks of ten, to receive the H pylori vaccine or placebo. Participants, their guardians, and study investigators were masked to treatment allocation. The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination. We did analysis in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT02302170.

Findings: Between Dec 2, 2004, and March 19, 2005, we randomly assigned 4464 participants to either the vaccine group (n=2232) or the placebo group (n=2232), of whom 4403 (99%) participants completed the three-dose vaccination schedule and were included in the per-protocol efficacy analysis. We extended follow-up to 3 years. We recorded 64 events of H pylori infection within the first year (14 events in 2074·3 person-years at risk in the vaccine group vs 50 events in 2089·6 person-years at risk in the placebo group), resulting in a vaccine efficacy of 71·8% (95% CI 48·2-85·6). 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction. Serious adverse events were reported in five (<1%) participants in the vaccine group and seven (<1%) participants in the placebo group, but none was considered to be vaccination related.

Interpretation: The oral recombinant H pylori vaccine was effective, safe, and immunogenic in H pylori-naive children. This vaccine could substantially reduce the incidence of H pylori infection; however, follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases.

Funding: Chongqing Kangwei Biological Technology.
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http://dx.doi.org/10.1016/S0140-6736(15)60310-5DOI Listing
October 2015
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