Jianwen Situ

University of Hong Kong

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Siddharth Sridhar

Janssen (Germany)

Jian‐Piao Cai

South China Sea Institute Of Oceanology

Shusheng Wu

University of Hong Kong

Kwok‐Yung Yuen

University of Hong Kong

Nicholas Foo‐Siong Chew

University of Hong Kong

Wenhai Yu

Chinese Academy of Medical Sciences & Peking Union Medical College

Estie Hon-Kiu Shun

University of Hong Kong

Vincent Chi‐Chung Cheng

Queen Mary Hospital

Fen Huang

Kunming University of Science and Technology

Cuiting Luo

Sun Yat-sen University

Cooperative Institutions

University of Hong Kong

Chinese University of Hong Kong

Queen Mary Hospital

Kunming University of Science and Technology

HKU-Pasteur Research Pole

Hong Kong Science and Technology Parks Corporation

Chinese Academy of Sciences

Xuzhou Medical College

University of Hong Kong - Shenzhen Hospital

Xiamen University

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Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant

Frontiers in Cellular and Infection Microbiology (2023)

Kun Wen Jian‐Piao Cai Xiaodi Fan Xiaojuan Zhang Cuiting Luo

Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model.Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant.Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

spike protein

10.3389/fcimb.2023.1213806

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Citations (1)

Redeveloping antigen detection kits for the diagnosis of rat hepatitis E virus

Journal of Clinical Microbiology (2023)

Zihao Chen Guanghui Li Jianwen Situ Zhiyong Li Shaoqi Guo

The emergence of

Hepatitis E Virus

Hepatitis E

Caliciviridae

10.1128/jcm.00710-23

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Citations (4)

Sex-specific associations between exclusive breastfeeding and postpartum depression in Chinese women

BMC Pregnancy and Childbirth (2024)

Liping Meng Mingyang Wu Jianwen Situ Yong Gu Songxu Peng

Depression

10.1186/s12884-024-07045-2

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Risk of Hepatitis E among Persons Who Inject Drugs in Hong Kong: A Qualitative and Quantitative Serological Analysis

Microorganisms (2020)

Siddharth Sridhar Nicholas Foo‐Siong Chew Jianwen Situ Shusheng Wu E. Chui

Hepatitis E virus (HEV) is an important cause of hepatitis, which can be transmitted via the bloodborne route. However, risk of hepatitis E among persons who inject drugs (PWIDs) is poorly understood. This study aimed to elucidate whether PWIDs are at risk for hepatitis E. We performed HEV IgM, IgG and nucleic acid detection on a cohort of 91 PWIDs and 91 age- and sex-matched organ donors. Blood HEV IgG was measured using the WHO HEV antibody standard. The effects of age, gender and addictive injection use on HEV serostatus and concentration were assessed. HEV IgG seroprevalence was 42/91 (46.2%) in the PWID group and 20/91 (22%) in the donor group (odds ratio = 3.04 (1.59–5.79), p = 0.0006). The median HEV IgG concentration was 5.8 U/mL (IQR: 2.5–7.9) in the PWID group and 2.1 U/mL (IQR: 1.2–5.3) in the donor group (p = 0.005). Increasing age and addictive injection use were significantly associated with HEV IgG serostatus, but only addictive injection use was associated with HEV IgG concentration (p = 0.024). We conclude that PWIDs are at increased risk for hepatitis E and are prone to repeated HEV exposure and reinfection as indicated by higher HEV IgG concentrations.

Serostatus

Hepatitis E Virus

Seroprevalence

Hepatitis E

Viral Hepatitis

10.3390/microorganisms8050675

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Citations (4)

Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy

Journal of Hepatology (2021)

Siddharth Sridhar Jianwen Situ Jian‐Piao Cai Cyril Chik‐Yan Yip Shusheng Wu

Antigenicity

10.1016/j.jhep.2020.12.028

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Citations (45)

Hepatitis E Virus Species C Infection in Humans, Hong Kong

Clinical Infectious Diseases (2021)

Siddharth Sridhar Cyril Chik Yan Yip Kelvin Hon Yin Lo Shusheng Wu Jianwen Situ

Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus species C genotype 1 (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals.A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between 1 August 2019 and 31 December 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed.HEV-C1 accounted for 8 of 53 (15.1%) reverse-transcription polymerase chain reaction (RT-PCR)-confirmed HEV infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV immunoglobulin M. Cumulatively, HEV-C1 accounted for 9 of 21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9 [77.8%]) as HEV-A patients (10/12 [75%]). HEV-C1 patients responded to oral ribavirin, although response to first course was sometimes poor or delayed.Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option.

Hepatitis E Virus

Hepatitis E

Caliciviridae

Zoonosis

10.1093/cid/ciab919

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Citations (66)

Bonding Performance of Asphalt-Aggregate Interface and the Predictive Model of Raveling in Ogfc Layers

SSRN Electronic Journal (2022)

Kailing Deng Duanyi Wang Cheng Tang Hui Li Jianwen Situ

Raveling is the most common distress of the Open Graded Friction Course (OGFC). It is mainly attributed to the poor bonding performance of asphalt and aggregate, and can decrease durability and reduce the service life of OGFC layers. A new test method, Pendulum Impact Test, was used to analyze the bonding performance of asphalt and aggregate. The effects of temperature, type of asphalt, type of aggregate, and moisture were studied. The results showed that the bonding energy presented an approximate parabolic change with temperature, and adhesive failure played a significant role at low temperatures, while cohesive failure was the dominant failure mode at high temperatures. In addition, the type of asphalt and moisture condition also significantly impacted the test results. Also, a cumulative damage model of the asphalt-aggregate interface was built based on experimental data using energy dissipation theory. According to the model, the cumulative damage to the asphalt-aggregate interface presented an increasing trend of superimposed linear and cosine variation with time, and increased sharply with load frequency followed by a tendency of flattening out. Â Hopefully, it can provide a theoretical basis for predicting the development of raveling and valuable suggestions for the design and maintenance of OGFC layers .

Asphalt pavement

Interface (matter)

Interface model

10.2139/ssrn.4100177

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A cumulative damage model for predicting and assessing raveling in asphalt pavement using an energy dissipation approach

Frontiers of Structural and Civil Engineering (2024)

Kailing Deng Duanyi Wang Cheng Tang Jianwen Situ Luobin Chen

Asphalt pavement

10.1007/s11709-024-1074-2

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Citations (2)

High prevalence of hepatitis E virus in semen of infertile male and causes testis damage

Gut (2017)

Fen Huang Feiyan Long Wenhai Yu Jianwen Situ Lijie Fu

We read with interest the paper by Todt et al 1 concerning the mutagenesis of Hepatitis E virus (HEV) caused by ribavirin treatment. HEV is a major cause of acute hepatitis worldwide and lacks a specific treatment.1 2 It replicates in many extrahepatic sites (spleen, kidney, brain and muscle3–5), but whether the testis is included is unknown. Active HEV has been detected in body fluids (blood,2 urine4 and milk6), but no report exists for semen. Thus, HEV prevalence in the semen of infertile males (n=185) sexually abstinent for at least 2 days was investigated by reverse transcriptase-PCR. Ethical approval was obtained from the Institutional Ethics Committee. Unexpectedly, 28.11% (52/185) of the males were HEV RNA positive (HEV RNA+; detectable HEV ORF1 and ORF2 were considered as HEV RNA+, figure 1A) with comparable viral titers to that from urine (see figure S1 in the online supplementary file 1). The prevalence of HEV in semen was higher in infertile males than in serum of pregnant women (1.82%) or the general population (0.58%) in the same city. ### Supplementary file 1 [SP1.pdf] Figure 1 (A) Positive rate of Hepatitis E virus (HEV) RNA in the semen of …

Hepatitis E Virus

Sexual transmission

10.1136/gutjnl-2017-314884

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Citations (36)

Hepatitis E viral infection causes testicular damage in mice

Virology (2019)

Jianwen Situ Wenjing Wang Feiyan Long Weimin Yang Chenchen Yang

Hepatitis E Virus

Sex organ

10.1016/j.virol.2019.12.009

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Citations (19)