Publications by authors named "Wei-Jin Huang"

12 Publications

  • Page 1 of 1

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

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.

Signal Transduct Target Ther 2021 03 27;6(1):134. Epub 2021 Mar 27.

Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
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http://dx.doi.org/10.1038/s41392-021-00558-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997800PMC
March 2021

A Thermostable mRNA Vaccine against COVID-19.

Cell 2020 09 23;182(5):1271-1283.e16. Epub 2020 Jul 23.

Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China. Electronic address:

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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http://dx.doi.org/10.1016/j.cell.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377714PMC
September 2020

A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.

Cell Host Microbe 2020 07 27;28(1):124-133.e4. Epub 2020 May 27.

Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. Electronic address:

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.
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http://dx.doi.org/10.1016/j.chom.2020.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250783PMC
July 2020

Author Correction: Craniometrics Reveal "Two Layers" of Prehistoric Human Dispersal in Eastern Eurasia.

Sci Rep 2019 May 23;9(1):7984. Epub 2019 May 23.

Commission for the Archaeology of Noneuropean Cultures of the German Archaeological Institute, 53173, Bonn, Germany.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-44355-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531514PMC
May 2019

Craniometrics Reveal "Two Layers" of Prehistoric Human Dispersal in Eastern Eurasia.

Sci Rep 2019 02 5;9(1):1451. Epub 2019 Feb 5.

Commission for the Archaeology of Noneuropean Cultures of the German Archaeological Institute, 53173, Bonn, Germany.

This cranio-morphometric study emphasizes a "two-layer model" for eastern Eurasian anatomically modern human (AMH) populations, based on large datasets of 89 population samples including findings directly from ancient archaeological contexts. Results suggest that an initial "first layer" of AMH had related closely to ancestral Andaman, Australian, Papuan, and Jomon groups who likely entered this region via the Southeast Asian landmass, prior to 65-50 kya. A later "second layer" shared strong cranial affinities with Siberians, implying a Northeast Asian source, evidenced by 9 kya in central China and then followed by expansions of descendant groups into Southeast Asia after 4 kya. These two populations shared limited initial exchange, and the second layer grew at a faster rate and in greater numbers, linked with contexts of farming that may have supported increased population densities. Clear dichotomization between the two layers implies a temporally deep divergence of distinct migration routes for AMH through both southern and northern Eurasia.
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http://dx.doi.org/10.1038/s41598-018-35426-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363732PMC
February 2019

[Evaluation on the analytical sensitivity of 31 HBsAg enzyme immunoassay kits].

Zhonghua Liu Xing Bing Xue Za Zhi 2009 Aug;30(8):841-4

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China.

Objective: To study the analytical sensitivity on 31 HBsAg enzyme immunoassy (EIA) test kits.

Methods: Thirty one HBsAg EIA kits produced by domestic or overseas manufactories and applied for approval during May 2007 to May 2008, were evaluated using the national reference panels. The hyperbolic curve of the log A value and log concentration for the national sensitivity standards was established. The cut-off value of each kit was substituted into the curvilinear equation to determine the analytical sensitivity which was compared between different HBsAg EIA kits.

Results: Twenty seven (351 lots) domestic and 4 (27 lots) overseas kits were compared. Among 378 lots of the 31 HBsAg EIA kits, only 2 lots of the domestic kits had a lower sensitivity when tested with the national HBsAg reference panels, with an average approvalr ate of 99.43% (349/351). The mean analytical sensitivity of the domestic kits for adr, adw, ay serotypes were 0.307, 0.419, 0.513 ng/ml, respectively. There was a significant difference between serotypes (F = 97.30, P < 0.01). The mean analytical sensitivity of the overseas kits for adr, adw, ay serotypes were 0.054, 0.066, 0.050 ng/ml respectively, with no significant difference between serotypes (F = 0.65, P > 0.05). The analytical sensitivity of the overseas kits for all the three serotypes was higher than that of the domestic kits (P < 0.01). There was no significant difference found between the analytical sensitivities of the kits produced by the same manufactory using 30- or 60-minute incubation of detection (P > 0.05). In contrast, there was significant difference noticed between the analytical sensitivities of the kits produced by the same manufactory when tested for 10 or 15-minute coloration of the results (P < 0.01).

Conclusion: Analytical sensitivity of the HBsAg EIA domestic kits should be further improved, especially for detecting adw and ay serotypes.
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August 2009

[Genetic characterization of enterovirus 71 complete genome isolated in Beijing, 2008].

Zhonghua Liu Xing Bing Xue Za Zhi 2009 Jul;30(7):729-32

National Institute for Control of Pharmaceutical and Biological Products, Beijing, China.

Objective: To investigate the characterization of the complete genome of EV71 in Beijing, 2008 and to provide basis for selecting appropriate virus strain to develop vaccine.

Methods: 12 throat swab samples were collected from children with hand-foot-mouth disease (HFMD). One sample named 08YM-3 was cultured and isolated in vero cells. Viral RNA was extracted and carried out by RT-PCR and 5', 3' rapid amplification of cDNA ends (RACE) to obtain the sequence from 08YM-3. PCR products were cloned and analyzed. Nucleotide identity between sequences was calculated and sequence alignments were made to generate phylogenetic trees using MegAlign in DNAStar.

Results: 3 clones were constructed that covered EV71 complete genome. Data from sequences analysis showed that this viral strain named BJ08 shared 95.6%-96.7%, 88.3%-96.1%, 78.1%-94.0%, 90.8%-94.6%, 85.9%-94.1% and 90.9%-93.9% in 5' UTR, P1, P2, P3, 3' UTR region and complete genome with C4 subtype, respectively. BJ08 showed low nucleotides identity (<90%) with other subtypes. Phylogenetic trees established from alignment of the complete genome and VP1 region indicated that BJ08 belonged to C4 subtype. BJ08 and C4 subtype strains shared the same amino acids in 6 sites in VP1 region, which were associated with EV71 subtype. There was no mutation in VP1 antigen epitope (92-107aa).

Conclusion: This BJ08 strain belonged to C4 subtype. Further study on EV71 complete genome would have great significance for vaccine research.
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July 2009

[Evaluation of multiplex nucleic acid testing assays for screening of hepatitis B virus DNA in blood donation process].

Zhonghua Liu Xing Bing Xue Za Zhi 2008 Dec;29(12):1240-2

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China.

Objective: To evaluate the multiplex nucleic acid testing (NAT) assays for HBV, HCV and HIV in detecting HBV DNA in plasma samples.

Methods: 534 plasma samples collected form several areas were detected with Abbott Architect i2000 HBsAg, ani-HBs, HBeAg, anti-HBe, anti-HBc and anti-HBc IgM diagnostic kits. HBV DNA levels of those samples were detected with Roche COBAS AmpliPrep/COBAS TaqMan HBV Test. Two kinds of multiplex NAT assays for HBV, HCV and HIV were used to test HBV DNA of those 534 samples. Results of serology-markers and quantitative HBV DNA levels with results of NAT were compared.

Results: HBV DNA was positive in all 81 HBsAg, HBeAg and anti-HBc positive samples, detected by both of NAT assays. HBV DNA was positive in 11 and 19 of 200 HBsAg negative samples when detected with the two kinds of NAT assays separately. Compared with the quantitative results detected by Roche COBAS AmpliPrep/COBAS TaqMan HBV Test, the HBV DNA positive rates were 96.9% and 94.3% in 193 samples of HBV DNA levels over 500 IU/ml while 40.2% and 45.3% in 117 samples of HBV DNA levels below 500 IU/ml while 99.3% and 96.0% in 151 samples of DNA negative HBV.

Conclusion: There are some occult low level HBV DNA carriers with HBsAg negative results in China. NAT assays for HBV, HCV and HIV may be useful to improve the transfusion safety.
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December 2008

[Sensitivity and specificity of 4 domestic ELISA kits for detection of hepatitis B virus markers].

Zhonghua Liu Xing Bing Xue Za Zhi 2008 Sep;29(9):915-8

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China.

Objective: To compare and analyze the sensitivity, specificity of 4 domestic ELISA kits for detection of hepatitis B virus (HBV) markers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc).

Methods: Five hundred and ninety four serum samples collected from patients with chronic hepatitis B and abnormal blood donors were detected for HBV markers and by 4 domestic ELISA kits. Samples with conflicting results by different diagnostic kits were retested. Samples with the HBsAg values close to the cut-off point were detected by Abbott HBsAg confirmation kit (Architect HBsAg confirm). Sensitivity of the kits was determined, using the national sensitivity reference panels for HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc.

Results: The rates of sensitivity on 4 domestic kits for detection of HBsAg were 4 to 10 times lower, and on the 4 domestic kits for detection of anti-HBs, HBeAg, anti-HBe and anti-HBc were 4 to 16 times lower, as compared to Abbott Architect kits. In addition, the domestic HBV ELISA kits had some false positive results. The total coincidence rates of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc were 96.46%-98.15%, 94.28%-98.15%, 98.15%-99.49%, 90.07%-96.30%, 92.09%-96.80%, respectively.

Conclusion: Both sensitivity and specificity of the domestically produced HBV ELISA kits should be improved.
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September 2008

[Primary evaluation of anti-HEV diagnostic reagent by experimental infection animal model with hepatitis E virus].

Zhonghua Liu Xing Bing Xue Za Zhi 2008 Jan;29(1):48-51

National Institute for the Control of Pharmaceutical and Biological Product, Beijing 100050, China.

Objective: To evaluate anti-HEV diagnostic kits by experimental infecting rhesus monkeys with HEV.

Methods: Eight rhesus monkeys were infected with genotype 1 and 4 HEV separately. The alanine aminotransferase (ALT) level of all monkeys were detected before and after the process of infection. HEV RNA in stool specimens was tested by reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Anti-HEV IgG in serum was detected by GL-IgG and WT-IgG.

Results: HEV RNA presented in the stool of all the 8 monkeys after infection. The ALT level of 1 monkey infected with genotype 1 HEV and 2 monkeys infected with genotype 4 HEV appeared abnormally after infection. Tested by GL-IgG, 2 of the 4 monkeys infected with genotype 1 HEV and 1 of 4 monkeys infected with genotype 4 HEV seroconverted to anti-HEV IgG. However, when tested by WT-IgG, all the infected monkeys seroconverted to anti-HEV IgG. The anti-HEV IgG tested by WT-IgG was positive during the whole observation period,and the anti-HEV IgG measured by GL-IgG only remained 12 weeks after infection. Detected by GL-IgG and WT-IgG, seropositive conversion of the anti-HEV IgG happened almost at the same time.

Conclusion: Both GL-IgG and WT-IgG could detect the anti-HEV IgG of experimentally infected rhesus monkeys but the WT-IgG had a higher sensitivity for detection of anti-HEV IgG than
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January 2008

[Expression of HBV S and preS1 fusion gene in Pichia pastoris expression system].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2005 Dec;19(4):366-9

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China.

Background: To clone and express the ss1 recombinant gene containing S gene and preS1 (10-50 AA) gene in P. pastoris expression system.

Methods: The fusion gene ss1 containing the S (1-222 AA) gene and preS1 (10-50 AA) gene was constructed with PCR method. The fusion ss1 gene was cloned into the expression vector of pPIC3.5k. The linear vector DNA was transformed into the host cell of GS115 with electroporation method. After screening with G418, the product was induced to express with methanol and its antigenicity was analyzed.

Results: The molecular weight of expressed ss1 protein was about 30,000 dalton. The product was reactive to anti-HBs and anti-preS1 mAb.

Conclusion: The fusion gene was efficiently expressed in P. pastoris expression system.The expressed products have the antigenicity of both S and preS1 protein.
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December 2005