Publications by authors named "Feng-Cai Zhu"

109 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

Waning immunity and potential asymptomatic infection in 3-7 years old children who received one dose of measles-mumps-rubella vaccine: A 4-year prospective study.

Vaccine 2021 06 13;39(26):3509-3515. Epub 2021 May 13.

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Expanded Programme on Immunization, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China. Electronic address:

Background: Mumps outbreaks in adolescents who received two doses of measles-mumps-rubella vaccine (MMR) during childhood have been reported worldwide. In China, one dose of MMR administered in children aged among 18-24 months has a limited effect on the mumps epidemic. There are limited prospective studies evaluating the mumps immunity profile of children aged 3-7 years who received one dose of MMR. This study aimed to describe mumps immunity profile over a span of 4-years in kindergarten and primary school children.

Methods: An observational, prospective study on one-dose MMR in children aged 3-7 years who underwent blood sample collection in 2015, 2016, and 2018 was conducted from 2015 to 2018. The seropositivity and geometric mean concentration of mumps IgG antibodies over time were analyzed.

Results: A total of 3346 eligible children aged 3-7 years who underwent three rounds of blood sample collection were included. The overall seropositivity (79.6%) in 2015 was significantly higher than those recorded in 2016 (73.1%) and 2018 (71.4%). Approximately 11.6-15.9% of the participants were seropositive for mumps in 2015, and converted to negative in 2016. Meanwhile, 11.1-14.6% of the participants were seropositive for mumps in 2016, and the results converted to negative in 2018. Over 6.1-7.4% of the participants had asymptomatic infection from 2015 to 2016, while 9.0-9.9% of the participants were infected without clinical symptoms from 2016 to 2018.

Conclusions: Kindergarten and primary school children who only received one dose of MMR were at higher risk of developing mumps. Waning immunity, seronegative conversion, and asymptomatic infection coexist in children who received one dose MMR. Determining the optimal age for administering the second dose of MMR in children should be prioritized to improve the control and prevention of mumps in China.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.008DOI Listing
June 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

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

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Emerg Microbes Infect 2021 Dec;10(1):365-375

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics, School of Public Health, Xiamen University, Xiamen, People's Republic of China.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.
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http://dx.doi.org/10.1080/22221751.2021.1891002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928063PMC
December 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

Safety and immunogenicity of meningococcal (Groups A and C) polysaccharide vaccine in children 2 to 6 y of age in China: a randomized, active-controlled, non-inferiority study.

Hum Vaccin Immunother 2021 03 3;17(3):919-926. Epub 2020 Dec 3.

Sanofi Pasteur, Lyon, France.

Meningococcal serogroups A and C cause significant numbers of cases in China. The Sanofi Pasteur meningococcal polysaccharide A + C vaccine (Men-AC) was licensed in China in 1995. Immunogenicity and safety of a single dose of Men-AC against a similar marketed vaccine, the Lanzhou Institute serogroups A and C vaccine (Lanzhou-AC), were evaluated in children 2 to 6 y of age. Antibody titers were determined before and on Day 30 after vaccination using a serum bactericidal assay using baby rabbit complement (SBA-BR). Immunogenicity endpoints included rates of seroconversion (postvaccination antibody titers ≥4-fold higher) and seroprotection (postvaccination titers ≥1:8). Unsolicited systemic adverse events (AEs) within 30 minutes after vaccination, solicited injection site and systemic reactions between Days 0 and 7, unsolicited non-serious AEs within 30 d, and serious adverse events (SAEs) throughout were recorded. Seroconversion rates against serogroups A and C were 97.0% (95% confidence interval [CI], 94.5-98.6) and 94.7% (95% CI, 91.6-97.0), respectively, in the Men-AC group and 97.7% (95% CI, 95.4-99.1) and 94.8% (95% CI, 91.7-97.0), respectively, in the Lanzhou-AC group, while seroprotection rates were 98.0% (95% CI, 95.8-99.3) and 97.0% (95% CI, 94.5-98.6), respectively, in the Men-AC group and 99.0% (95% CI, 97.2-99.8) and 96.8% (95% CI, 94.1-98.4), respectively, in the Lanzhou-AC group. Non-inferiority of Men-AC with regard to immunogenicity was demonstrated since the lower bounds of the 95% CIs of the differences in rates between the two groups were > -5% for both serogroups. Both vaccines were well tolerated.
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http://dx.doi.org/10.1080/21645515.2020.1801077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993220PMC
March 2021

Structure-based development of human antibody cocktails against SARS-CoV-2.

Cell Res 2021 01 1;31(1):101-103. Epub 2020 Dec 1.

CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

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http://dx.doi.org/10.1038/s41422-020-00446-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705432PMC
January 2021

Challenges in the Development of a Vaccine Against COVID-19.

Engineering (Beijing) 2020 Oct 14;6(10):1067-1069. Epub 2020 Sep 14.

Jiangsu Provincial Center of Disease Control and Prevention, Nanjing 210009, China.

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http://dx.doi.org/10.1016/j.eng.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489243PMC
October 2020

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

Influenza surveillance in China: a big jump, but further to go.

Lancet Public Health 2019 09;4(9):e436-e437

Key Laboratory of Enteric Pathogenic Microbiology (National Health Commission), Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China; Center for Global Health, Nanjing Medical University, Nanjing, China. Electronic address:

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http://dx.doi.org/10.1016/S2468-2667(19)30158-6DOI Listing
September 2019

Efficacy, immunogenicity and safety of the AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years: End-of-study results from a phase II/III, randomised, controlled trial.

Cancer Med 2019 10 15;8(14):6195-6211. Epub 2019 Jul 15.

GSK, Wavre, Belgium.

Background: Cervical cancer is a major public health concern in China. We report the end-of-study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04-human papillomavirus (HPV)-16/18 vaccine in Chinese women aged 18-25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported.

Methods: Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of AS04-HPV-16/18 vaccine or Al(OH) (control) at Months 0-1-6. Vaccine efficacy against HPV-16/18 infection and cervical intraepithelial neoplasia (CIN), cross-protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according-to-protocol efficacy (ATP-E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC-E; vaccine N = 2987; control N = 2985) and TVC-naïve (vaccine N = 1660; control N = 1587).

Results: In initially HPV-16/18 seronegative/DNA-negative women, vaccine efficacy against HPV-16/18-associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP-E, 88.7% (95% CI: 18.5, 99.7) in the TVC-E, and 100% (95% CI: 17.9, 100) in the TVC-naïve. Cross-protective efficacy against incident infection with HPV-31, HPV-33 and HPV-45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP-E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and anti-HPV-18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group.

Conclusions: This is the first large-scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV-16/18-associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China.

Trial Registration: NCT00779766.
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http://dx.doi.org/10.1002/cam4.2399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797633PMC
October 2019

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women.

Sci China Life Sci 2020 Apr 21;63(4):582-591. Epub 2019 Jun 21.

The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen, 361102, China.

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.
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http://dx.doi.org/10.1007/s11427-019-9547-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223315PMC
April 2020

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

J Natl Cancer Inst 2020 02;112(2):145-153

Funing Center for Disease Control and Prevention, Funing, Jiangsu, China.

Background: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.

Methods: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.

Results: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.

Conclusions: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.
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http://dx.doi.org/10.1093/jnci/djz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019098PMC
February 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

Severe human infection with a novel avian-origin influenza A(H7N4) virus.

Sci Bull (Beijing) 2018 Aug 19;63(16):1043-1050. Epub 2018 Jul 19.

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

Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets (LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry (chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.
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http://dx.doi.org/10.1016/j.scib.2018.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104738PMC
August 2018

Seroepidemiology of Coxsackievirus A10 infection in infants and children: A prospective cohort study in Jiangsu, China.

J Infect 2018 08 7;77(2):158-164. Epub 2018 May 7.

National Institutes for Food and Drug Control, Beijing 102629, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2018.04.005DOI Listing
August 2018

Waning immunity of one-dose measles-mumps-rubella vaccine to mumps in children from kindergarten to early school age: a prospective study.

Expert Rev Vaccines 2018 05 12;17(5):445-452. Epub 2018 Mar 12.

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

Background: In China, one dose measles-mumps-rubella vaccine (MMR) was administered to children aged 18-24 months. The mumps incidence was still high. Data on the waning immunity to mumps after MMR vaccination are limited. This study aimed to describe the waning immunity to mumps in kindergarten and primary school children to provide a scientific basis for confirming an optimal age for a second dose.

Methods: An observational, prospective study on one-dose MMR in children in kindergarten and primary school was conducted from 2015 to 2016. Waning immunity to mumps in terms of seropositivity and geometric antibody concentration (GMC) with time was analyzed.

Results: In total, 7436 eligible subjects in kindergarten (3435) and primary school (4001) were included in 2015. The overall GMC (201.7 U/ml) and seropositivity (75.4%) to mumps antibodies in 2016 were significantly lower compared to those in 2015 (218.7 U/ml, 78.4%). Asymptomatic infection occurred within one year in 8.8% of children who received one-dose MMR.

Conclusions: Children who received one-dose MMR in kindergarten and primary school were at high risk of mumps infection, and waning immunity occurred with time. Determining the optimal age for the second dose of MMR in children should be prioritized to prevent mumps epidemics.
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http://dx.doi.org/10.1080/14760584.2018.1445529DOI Listing
May 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

The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study.

Vaccine 2018 01 28;36(2):256-263. Epub 2017 Nov 28.

Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

Background/aims: A birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV.

Methods: From 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months.

Results: Maternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407).

Conclusions: One birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.
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http://dx.doi.org/10.1016/j.vaccine.2017.11.037DOI Listing
January 2018

The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China.

Vaccine 2017 12 1;35(48 Pt B):6627-6633. Epub 2017 Nov 1.

Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

Background: Antiviral therapy has been documented to reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic mothers. This large prospective cohort study conducted in China aims to delineate the maternal viral threshold for consideration of antiviral prophylaxis in settings with limited resources.

Methods: A total of 1177 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current passive-active prophylaxis regimen were enrolled from community health centers in Jiangsu and Henan provinces, China. Maternal hepatitis B e antigen (HBeAg) status and viral load were tested at 36-40 weeks of gestation. Post-vaccination serologic testing was performed at 7 and 12 months of age.

Results: HBeAg-positive mothers (419/1177; 35.6%) had significantly higher viral loads, compared with HBeAg-negative mothers (758/1177; 64.4%) (8.12 vs. 2.69 log IU/mL, p < .0001). Twenty infants, born to HBeAg-positive mothers with high viral loads (median, 8.38; range: 7.82-9.22 log IU/mL), were infected at 7 months of age. In contrast, none of the HBeAg-negative mothers transmitted HBV to their offspring. After adjustment for the other risk factor, a higher maternal viral load was significantly associated with a higher risk of transmission (adjusted odds ratio, 3.78; 95% confidence interval: 1.46-9.81; p = .006). The rates of passive-active immunoprophylaxis failure were 0.0% (0/789), 0.0% (0/27), 0.0% (0/32) and 6.1% (20/329) at maternal viral loads of <5, 5-6, 6-7 and ≥7 log IU/mL, respectively. The antibody to hepatitis B surface antigen (anti-HBs) response rate was 98.4% (1138/1157) at 7 months of age.

Conclusions: Results from this study indicate that the maternal viral threshold associated with perinatal transmission of HBV is 7 log IU/mL, which may be appropriate for consideration of antiviral prophylaxis in settings with limited resources.
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http://dx.doi.org/10.1016/j.vaccine.2017.10.032DOI Listing
December 2017

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

A phase 1 randomized open-label clinical study to evaluate the safety and tolerability of a novel recombinant hepatitis E vaccine.

Vaccine 2017 09 10;35(37):5073-5080. Epub 2017 Aug 10.

College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, Jilin, China; Key Laboratory for Zoonosis, Ministry of Education, and Institute for Zoonosis of Jilin University, Changchun 130062, Jilin, China. Electronic address:

Background: This study aimed to evaluate the safety and tolerability for variable dosages of a novel hepatitis E vaccine p179.

Methods: The randomized open-label parallel control phase 1 clinical trial enrolled 120 eligible participants aged 16-65years in Jiangsu Province, China. The experimental groups were randomized to receive different dosages of 20μg, 30μg, and 40μg Hepatitis E Virus (HEV) p179 vaccines, with the 30μgHEV vaccine p239 Hecolin as control, and vaccinated at 0, 1 and 6month intervals. Participants were observed for solicited local and systemic adverse reactions (ARs) occurring within 7days after each vaccination, and any serious adverse events (SAEs) occurring within 6months post-vaccination. Blood samples were collected from participants 3days before and after each injection, to determine the blood routine and serum biochemical indexes.

Results: The solicited local ARs incidence in experimental groups were significantly lower than that of the control group (P=0.027). The difference between solicited total and systemic ARs incidence of experimental groups and the control group were not significant (P>0.05). Similar patterns were observed when the analyses were performed on the group having ARs of varying grades and symptoms. All changes in blood biochemical indexes and routine blood tests before and after different vaccinations were mild (grade 1) or moderate (grade 2), and the difference in experimental groups and the control group were not statistically significant. No vaccine related SAEs occurred in any of the subjects during the study.

Conclusion: Three different dosages of HEV p179 vaccine were deemed safe and well tolerated. No vaccine-associated SAEs were identified, and the 30μg dosage formulation was selected for further investigation for efficacy. Clinical trials registration number: 2012L01657.
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http://dx.doi.org/10.1016/j.vaccine.2017.05.072DOI Listing
September 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
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