Publications by authors named "H J Huang"

27,928 Publications

Safety and immunogenicity of a recombinant adenovirus type-5-vectored COVID-19 vaccine with a homologous prime-boost regimen in healthy participants aged 6 years and above: a randomised, double-blind, placebo-controlled, phase 2b trial.

Clin Infect Dis 2021 Sep 22. Epub 2021 Sep 22.

Beijing Institute of Biotechnology, Beijing, China.

Background: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine with homologous prime-boost regimens in healthy participants aged 6 years and above.

Methods: In this randomised, double-blind, placebo-controlled trial, participants received low-dose vaccine, middle-dose vaccine or placebo. Prime-booster regimens were given intramuscularly 56 days apart. ELISA antibodies to the receptor binding domain (RBD) and pseudovirus neutralising antibodies were detected. Adverse events were monitored for 28 days following each vaccination.

Results: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 participants aged 56 years and older (OLD cohort), and 150 participants aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies which decreased with increasing age, with geometric mean titres (GMTs) of 1037.5 in MIN cohort, 647.2 in MID cohort, and 338.0 in OLD cohort receiving 5×10 10 viral particles on day 28 following boost vaccination. Pseudovirus neutralising antibodies showed a similar pattern, with GMTs of 168.0 in MIN cohort, 76.8 in MID cohort, and 79.7 in OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by two doses in adults, with GMTs of 1091.6 and 96.6 in ELISA antibody and neutralising antibody, respectively. Homologous prime-boost vaccination was safety and tolerable.

Conclusions: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.
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http://dx.doi.org/10.1093/cid/ciab845DOI Listing
September 2021

Simultaneous or prior activation of intrahepatic type I interferon signaling leads to hepatitis B virus persistence in a mouse model.

J Virol 2021 Sep 22:e0003421. Epub 2021 Sep 22.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

It remains controversial how interferon (IFN) response contributes to hepatitis B virus (HBV) control and pathogenesis. A previous study identified that hydrodynamic injection (HI) of type I IFN (IFN-I) inducer polyinosinic-polycytidylic acid (poly(I:C)) leads to HBV clearance in a chronic HBV mouse model. However, recent studies have suggested that premature IFN-I activation in the liver may facilitate HBV persistence. In the present study, we investigated how the early IFN-I response induces an immunosuppressive signaling cascade and thus causes HBV persistence. We performed HI of the plasmid adeno-associated virus (pAAV)/HBV 1.2 into adult BALB/c mice to establish an adult acute HBV replication model. Activation of the IFN-I signaling pathway following poly(I:C) stimulation or murine cytomegalovirus (MCMV) infection resulted in subsequent HBV persistence. HI of poly(I:C) with the pAAV/HBV 1.2 plasmid resulted in not only the production of IFN-I and the anti-inflammatory cytokine interleukin (IL)-10 but also the expansion of intrahepatic regulatory T cells (Tregs), Kupffer cells (KCs) and myeloid-derived suppressor cells (MDSCs), all of which impaired the T cell response. However, when poly(I:C) was injected at day 14 after the HBV plasmid injection, it significantly enhanced HBV specific T cell responses. In addition, interferon-alpha/beta receptor (IFNAR) blockade rescued T cell response by downregulating of IL-10 expression and decreasing Treg and KC expansion. Consistently, Treg depletion or IL-10 blockade also controlled HBV replication. IFN-I plays a double-edged sword role during chronic HBV infection. Here, we identified that application of IFN-I at different time points causes contrast outcome. Activation of the IFN-I pathway before HBV replication induces an immunosuppressive signaling cascade in the liver, and consequently caused HBV persistence while IFN-I activation post HBV infection enhances HBV-specific T cell responses and thus promote HBV clearance. This result provided an important clue to the mechanism of HBV persistence in adult individuals.
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http://dx.doi.org/10.1128/JVI.00034-21DOI Listing
September 2021

Kinetics of SARS-CoV-2 Specific and Neutralizing Antibodies over Seven Months after Symptom Onset in COVID-19 Patients.

Microbiol Spectr 2021 Sep 22:e0059021. Epub 2021 Sep 22.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (< 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.
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http://dx.doi.org/10.1128/Spectrum.00590-21DOI Listing
September 2021

Sandmeyer-Type Reductive Disulfuration of Anilines.

Org Lett 2021 Sep 22. Epub 2021 Sep 22.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Advanced Catalytic Engineering Research Center of the Ministry of Education, Hunan University, Changsha, Hunan 410082, People's Republic of China.

A transition metal/ligand-free disulfuration of anilines with disulfur transfer reagents (dithiosulfonate or tetrasulfide) is reported herein. The reaction, which can be considered as a reductive disulfuration variation of the classic Sandmeyer reaction, is performed under mild conditions and exhibits broad scope across the aniline substrate and disulfur transfer reagent classes. The gram-scale synthesis of disulfides is successfully achieved through this method, rendering the approach highly valuable.
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http://dx.doi.org/10.1021/acs.orglett.1c02636DOI Listing
September 2021

Preoperative Urine Analysis is an Effective Tool to Predict Fever after Miniaturized Percutaneous Nephrolithotomy on Large Renal Stones.

Urol J 2021 Sep 22. Epub 2021 Sep 22.

Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.

Purpose: To investigate the preoperative and intraoperative potential risk factors associated with miniaturized percutaneous nephrolithotomy (mPCNL) fever in the treatment of patients with large renal stones.

Materials And Methods: All patients with renal stones larger than 2.5 cm, who had also undergone mPCNL, were included in the period between April 2018 and September 2019. Logistic regression analyses were performed to identify clinical variables associated with post-operative fever (>38°C).

Results: A total of 53 patients were enrolled for whom the median maximal stone length was 3.08 cm. 24 (45%) patients had a fever after mPCNL. Significantly more patients with urine WBC ³ 27(/HPF) had a fever after surgery (p = 0.004). No significant between-group differences in urine cultures were found for the fever and non-fever groups (p=0.094). Stepwise and multivariable logistic regression analyses all revealed that urine WBC ³ 27(/HPF) is the only risk factor for developing post-mPCNL fever. Based on the highest body temperature, all of the patients were assigned into no fever, mild fever (37.5£ Temp < 38.0), and fever groups, and an ordinal logistic regression analysis still supported the premise that the result of urine analysis is strongly associated with post-mPCNL fever.

Conclusion: Large renal stones are challenging to treat and associated with severe complications. Approximately 45% of large renal stone patients treated via mPCNL developed a fever. Urine WBC can easily and directly predict the risk of fever.
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http://dx.doi.org/10.22037/uj.v18i.6463DOI Listing
September 2021
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