Prof. CHEN Zhiwei
DVM (Northwestern Agricultural University), MSc (New Mexico State University), PhD (New York University)
Director, AIDS Institute
Professor
Email: zchenai@hku.hk
ORCID : https://orcid.org/0000-0002-4511-2888
HKU Scholars Hub: https://hub.hku.hk/cris/rp/rp00243
Tel: (852) 3917 9831; Fax: 2817 7805
Office: Room 44, 5/F, Laboratory Block, 21 Sassoon Road, Pokfulam
RESEARCH DESCRIPTION
My major research interests are in the development of HIV-1-based vaccines for China and of a relevant animal model for vaccine testing and pathogenesis studies. My current focus is on the generation and characterization of multivalent AIDS vaccines using a live modified vaccinia Tiantan (MVTT) strain as well as novel strategies of antigen-targeting to dendritic cells (DC). For these purposes, I have designed and constructed several attenuated yet replicating MVTT vectors for better antigen delivery and vaccinia production. Using them, we were able to generate a single recombinant vaccinia MVTT virus to deliver three SIV genes (env and gag-pol). Preliminary testing in monkeys has shown that the virus can induce stronger cell-mediated and antibody responses to all three SIV gene products, which conferred significant protection against intrarectal SIVmac239 challenge. As a preventive means, I will further develop, optimize, and eventually test MVTT-based vaccine in humans in the near future. Meantime, we have successfully discovered a new way of antigen-targeting to dendritic cells. Using soluble PD1 as a targeting molecule, we were able to elicit high frequency of polyfunctional HIV Gag-specific CD8+ T cells, which confer significant protection against pathogenic viral infection and therapeutic cure of malignant mesothelioma in mice. For the assessment of the vaccine efficacy, I am also actively investigating HIV evolution in China. Doing this study over several years, we will gain crucial prevalent and incident rate data that will be essential for our future vaccine testing in humans. Furthermore, I have also established the first R5-dependent SHIV/macaque models using subtype C and B’ envelopes. Since these viruses can be transmitted to virus-naïve monkeys atraumatically via the intravaginal route, we can mimic the dominant mode of HIV-1 spread in humans and apply the model to relevant questions. For example, I will use this new animal model to test the efficacy of HIV subtype C Env-based vaccines. The model may also be used for cross-subtype challenge or microbicides testing. In addition, using vaccinia MVTT-based and novel antigen-targeting systems, we are constructing vaccines against SARS-CoV, Influenza and TB infections as well as immunotherapies against cancer.
professrional experience
2014 – present Director and Tenured Professor; AIDS Institute, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
2007 – 2014 Director and Tenure-track Associate Professor; AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
2002 – 2007 Guest Professor and Ph.D. Advisor, State Key Laboratory of Virology of China, Modern Virology Research Center and AIDS Center, College of Life Sciences, Wuhan University, China
2002 – 2007 Staff Investigator and Assistant Professor, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA
1999 – 2002 Research Scientist, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA (Mentor: Professor David D. Ho)
1996 – 1999 Postdoctoral Fellow, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA (Mentor: Professor David D. Ho)
selected publications
(*Corresponding author)
- Chen Z, Telfer P, Gettie A, Reed P, Zhang L, Ho DD and Marx PA. 1996. Genetic characterization of new West African simian immunodeficiency virus SIVsm: geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. Journal of Virology. 70:3617-3627, 1996.
- Chen Z, Luckay A, Sodora DL, Telfer P, Reed P, Gettie A, Kanu JM, Sadek RF, Yee J, Ho DD, Zhang L and Marx PA. Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus infected sooty mangabeys. Journal of Virology. 71:3953-3960, 1997.
- Chen Z, Zhou P, Ho DD, Landau NR and Marx PA. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. Journal of Virology. 71:2705-2714, 1997.
- Chen Z, Gettie A, Ho DD and Marx PA. Primary SIVsm isolates use the CCR5 co-receptor from sooty mangabeys naturally infected in West Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2 and SIVmac. Virology. 246:113-124, 1998.
- Chen Z, Kwon D, Jin Z , Monard S, Telfer P, Jones MS, Aguilar R, Ho DD and Marx PA. Natural infection of a homozygous deleted CCR5 red-capped mangabey with a CCR2b-tropic simian immunodeficiency virus. Journal of Experimental Medicine. Dec 7;188(11):2057-65, 1998.
- Chen Z, Huang Y, Zhao X, Skulsky E, Lin D, Ip J, Gettie A and Ho DD. Enhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina). Journal of Virology. 74:6501-10, 2000.
- Chen Z, Zhao X, Huang Y, Huang YL, Gettie A, Ba L, Blanchard J and Ho DD. CD4+ Lymphocytopenia in Acute Infection of Asian Macaques by a Vaginally Transmissible Subtype-C, CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV). Journal of Acquired Immune Deficiency Syndromes. 30:133-145, 2002.
- Su B, Liu L, Wang F, Gui X, Zhao M, Tien P, Zhang L and Chen Z*. HIV-1 subtype B’ dictates the AIDS epidemic among paid blood donors in the Henan and Hubei provinces of China. AIDS. 21;17(17):2515-20. 2003.
- Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, Wei Q, He T, Yu W, Yu J, Gao H, Tu X, Gettie A, Farzan M, Yuen KY, Ho DD. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. Journal of Virology. 79(5):2678-88. 2005.
- Fang Q, Yang L, Zhu W, Liu L, Wang H, Yu W, Xiao G, Tien P, Zhang L,Chen Z*. Host range, growth property, and virulence of the smallpox vaccine: vaccinia virus Tian Tan strain. Virology. 10;335(2):242-51. 2005.
- Yi CE, Ba L, Zhang L, Ho DD, Chen Z*. Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain. Journal of Virology. Sep;79(18):11638-46. 2005.
- Zhang Y, Lu L, Ba L, Liu L, Yang L, Jia M, Wang H, Fang Q, Shi Y, Yan W, Chang G, Zhang L, Ho DD, Chen Z*. Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China. PLoS Medicine. 2006 Nov;3(11):e443.
- Liu L, Fang Q, Deng F, Wang H, Yi C, Ba L, Yu W, Lin RD, Li T, Hu ZH, Ho DD, Zhang L, Chen Z*. Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. Journal of Virology. 2007. May;81(9):4694-700.
- Ba L, Yi CE, Zhang L, Ho DD, Chen Z*. Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus. Applied Microbiology and Biotechnology. 2007 Oct;76(5):1131-6.
- Chen Z, Huang Y, Zhao X, Ba L, Zhang W and Ho DD. Design, Construction, and Characterization of a Multigenic Modified Vaccinia Ankara Candidate Vaccine against Human Immunodeficiency Virus Type 1 Subtype C/B’. Journal of Acquired Immune Deficiency Syndromes. 2008 Apr 1;47(4):412-21.
- Chen YX, Liu L, Wei Q, Zhu H, Jiang H, Tu XM, Qin C and Chen Z*. Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques. Virology. 2008 Nov 10;381(1):89-97.
- Luo M, Liu H, Zhuang K, Liu L, Su B, Yang R, Tien P, Zhang L, Gui X and Chen Z*. Prevalence of drug resistant HIV-1 in rural areas of Hubei province in the People’s Republic of China. Journal of Acquired Immune Deficiency Syndromes. Jan 1; 50(1): 1-8. 2009.
- Huang XX, Lu B, Fang Q, Yu W, Liu L, Zhuang K, Shen TT, Wang HB, Tian P, Zhang L, and Chen Z*. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination. PLoS ONE. 2009;4(1):e4180.
- Xue H, Lu XF, Zheng PR, Liu L, Han CY, Hu JP, Liu ZJ, Ma T, Li Y, Wang L, Chen Z* and Liu G*. Highly suppressing wild-type HIV-1 and Y181C Mutant HIV-1 Strains by 10-Chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. Journal of Medicinal Chemistry. 53(3), pp1397-1401. 2010.
- Yu W, Fang Q, Zhu W, Wang H, Tien P, Zhang L, and Chen Z*. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT (ZCI) protects animals against pathogenic viral challenge. Vaccine. 2010 Feb 25;28(9):2088-96.
- Wang H, Zhuang K, Liu L, Tang Z, Tang J, Tien P, Zhang L, and Chen Z*. Acute infection of Chinese macaques by a CCR5-tropic SHIV carrying a primary HIV-1 subtype B’ envelope. Journal of Acquired Immune Deficiency Syndromes. Mar 1:53(3):285-291. 2010.
- Liu H, Yu W, Zhu W, Wang H, and Chen Z*. The route of inoculation determines the tissue tropism of modified vaccinia Tiantan expressing the spike glycoprotein of SARS-CoV in mice. Journal of Medical Virology. 2010 May;82(5):727-34.
- Liu L,Wei Q, Alvarez X, Wang H, Du Y, Zhu H, Jiang H, Zhou J, Lam P, Zhang L, Lackner A, Qin C, Chen Z*. Epithelial Cells Lining Salivary Gland Ducts Are Early Target Cells of Severe Acute Respiratory Syndrome Coronavirus Infection in the Upper Respiratory Tract of Rhesus Macaques. Journal of Virology. 2011. 85(8b):4025-4030.
- Lu B, Yu W, Huang XX, Wang H, Liu L, and Chen Z*. Mucosal immunization induces a higher level of lasting neutralizing antibody response in mice by a replication-competent smallpox vaccine, vaccinia Tiantan strain. Journal of Biomedicine and Biotechnology. 2011;2011:970424.
- Lu X, Liu L, Zhang X, Lau TC, Tsui SK, Kang Y, Zheng P, Zheng B, Liu G, Chen Z*. F18, a novel small molecule NNRTI, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Antimicrob Agents Chemother. 2012 Jan;56(1):341-51.
- Yao X, Wang H, Yan P, Lu Y, Lin H, Chen L, Ng J, Lau E, Li L, Wu J, Chen Z*. Rising epidemic of HIV-1 infections among general populations in Fujian, China. Journal of Acquired Immune Deficiency Syndromes. 2012 Jul; 60(3): 328-35.
- Kang Y, Wu Z,Lau TC, Lu X, Liu L, Cheung AK, Tan Z, Ng J, Liang J, Wang H, Li S, Zheng B, Li B, Chen L, Chen Z*. CCR5 antagonist TD-0680 uses a novel mechanism for enhanced potency against HIV-1 entry, cell-mediated infection, and a resistant variant. The Journal of Biological Chemistry. 2012 May; 287(20):16499-509.
- Zhou J, Cheung AKL, Tan Z, Wang H, Kang Y, Du Y, Lu X, Liu L, Yuen KY and Chen Z*. PD1-based DNA vaccine amplifies HIV-1 CD8+ T cells in mice. Journal of Clinical Investigation. 2013 Jul; 123(6):2629–2642..
- Sun C, Chen Z*, Tang X, Zhang Y, Feng L, Du Y, Xiao L, Liu L, Chen L, Zhang L. Mucosal Prime with a Replicating Vaccinia-based Vaccine Elicits Protective Immunity against SIV Challenge in Rhesus Monkeys. Journal of Virology. 2013 May; 87(10):5669-77. (Shared first author and corresponding author)
- Zhou J, Cheung AKL, Liu H, Tan Z, Tang X, Kang Y, Du Y, Wang H, Liu L, and Chen Z*. Potentiating functional antigen-specific CD8+ T cell immunity by a novel PD1 isoform-based fusion DNA vaccine. Molecular Therapy. 2013 Jul; 21(7):1445-55. .
- Peng Q, Wang H, Wang H, Li X, Lu X, Zhou B, and Chen Z*. Imbalances of gut-homing CD4+ T cell subsets in HIV-1 infected Chinese patients. Journal of Acquired Immune Deficiency Syndromes. 2013 Sep; 64(1):25-31.
- Xiao H, Liu L, Zhu Q, Tan Z, Yu W, Tang X, Zhan D, Du Y, Wang H, Liu D, Li Z, Yuen KY, Ho DD, Gao GF, Chen Z*. A replicating modified vaccinia tiantan strain expressing an avian-derived influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice. PLoS One. 2013 Dec 17;8(12):e83274.
- Tan Z, Zhou J, Cheung AK, Yu Z, Cheung KW, Liang J, Wang H, Lee BK, Man K, Liu L, Yuen KY, Chen Z*. Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. Cancer Research. 2014 Aug; 74:6010-21.
- Guo J, Zuo T, Cheng L, Wu X, Tang J, Sun C, Feng L, Chen L, Zhang L, Chen Z*. Simian immunodeficiency virus infection evades vaccine-elicited antibody responses to V2 region. Journal of Acquired Immune Deficiency Syndromes. 2015 Apr; 68(5):502-10.
- Cheng L, Tang X, Liu L, Peng J, Nishiura K, Cheung AK, Guo J, Wu X, Tang HY, An M, Zhou J, Cheung KW, Wang H, Guan X, Wu Z, Chen Z*. Monoclonal antibodies specific to human Δ42PD1: A novel immunoregulator potentially involved in HIV-1 and tumor pathogenesis. MAbs 2015 July; 7(3): 620-9.
- Zhe Y, Tan Z, Lee BK, Tang J, Wu X, Cheung KW, Lo NTL, Man K, Liu L, Chen Z*. Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells. Oncotarget. 2015 Oct; 6(32): 32426-38.
- Liu L, Wei Q, Nishiura K, Peng J, Wang H, Midkiff C, Alvarez X, Qin C, Lackner A and Chen Z*. Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques. Mucosal Immunology. 2016 Jul; 9(4):1089-101.
- Wu X, Liu L, Cheung KW, Wang H, Lu X, Cheung AK, Liu W, Huang X, Li Y, Chen ZW, Chen SM, Zhang T, Wu H, Chen Z*..Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice. Journal of Neuroimmune Pharmacology. 2016 Sep; 11(3):572-83.
- Wei Q, Liu L, Cong Z, Wu X, Wang H, Qin C, Molina P, Chen Z*. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin. Journal of Neuroimmune Pharmacology. 2016 Sep;11(3):584-591.
- Cheung A.K., Huang Y., Kwok H.Y., Chen M., Chen Z*. Latent human cytomegalovirus enhances HIV-1 infection in CD34+ progenitor cells. Blood Advances. 2017 Jan; 1(5):306-318.
- Cheung AK, Kwok HY, Huang Y, Chen M, Mo Y, Wu X, Lam KS, Kong HK, Lau TCK, Zhou J, Li J, Cheng L, Lee BK, Peng Q, Lu X, An M, Wang H, Shang H, Zhou B, Wu H, Xu A, Yuen KY, Chen Z*. Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection. Nature Microbiology. 2017 Oct;2(10):1389-1402.
- Tang X, Guo J, Cheng L, Sun C, Liu L, Zuo T, Wang H, Chen L, Zhang L, Chen Z*. Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses. Vaccine. 2017 May 2;35(19):2582-2591.
- Wu X, Guo J, Niu M, An M, Liu L, Wang H, Jin X, Zhang Q, Lam KS, Wu T, Wang H, Wang Q, Du Y, Li J, Cheng L, Tang HY, Shang H, Zhang L, Zhou P, Chen Z*. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. Journal of Clinical Investigation. 2018 Apr 23. pii: 96764.
- Liu W, Wong YC, Chen SMY, Tang J, Wang H, Cheung AKL, Chen Z*. DNA prime/MVTT boost regimen with HIV-1 mosaic Gag enhances the potency of antigen-specific immune responses. Vaccine. 2018 Jul 25;36(31):4621-4632.
- Cheung KW, Wu T, Ho SF, Wong YC, Liu L, Wang H, Chen Z*. α4β7 CD4 effector/effector memory T cells differentiate into productively and latently infected central memory T cells by transforming growth factor β1 during HIV-1 infection. Journal of Virology 2018 Mar 28;92(8). pii: e01510-17.
- Ling L, Tang X, Huang X, Li J, Wang H, Chen Z*. AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice. Journal of Neuroimmune Pharmacology. 2018 Dec;13(4):541-550.
- Tang J, Cai Y, Liang J, Tan Z, Tang X, Zhang C, Cheng L, Zhou J, Wang H, Yam WC, Chen X, Wang H, Chen Z*. In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge. Tuberculosis (Edinb). 2018 Dec;113:65-75.
- Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok HY, Tang HY, Nishiura K, Peng J, Tan Z, Wu T, Cheung KW, Chan KH, Alvarez X, Qin C, Lackner A, Perlman S, Yuen KY, Chen Z*. Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. Journal of Clinical Investigation Insight. 2019 Feb 21;4(4). pii: 123158.
- Ling L, Wu T, To KKW, Cheung KW, Lui KO, Niu M, Lam KS, Wang CC, Li J, Wang H, Yuen KY, Chen Z*. Vedolizumab-mediated integrin α4β7 blockade does not control HIV-1SF162 rebound after cART interruption in humanized mice. AIDS. 2019 Jan 14.
- Tan Z, Chiu MS, Yan CW, Wong YC, Huang H, Man K, Chen Z*. Anti-mesothelioma Immunotherapy by CTLA-4 Blockade Depends on Active PD1-Based TWIST1 Vaccination. Molecular Therapy Oncolytics. 2020;16:302-317.
- Liu L, To KK, Chan KH, Wong YC, Zhou R, Kwan KY, Fong CH, Chen LL, Choi CY, Lu L, Tsang OT, Leung WS, To WK, Hung IF, Yuen KY, Chen Z*. High neutralizing antibody titer in intensive care unit patients with COVID-19. Emerging Microbes & Infections. 2020 Jul;9(1):1664-1670. doi: 10.1080/22221751.2020.1791738.
- Zhou R, To KK, Wong YC, Liu L, Zhou B, Li X, Huang H, Mo Y, Luk TY, Lau TT, Yeung P, Chan WM, Wu AK, Lung KC, Tsang OT, Leung WS, Hung IF, Yuen KY, Chen Z*. Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses. Immunity. 2020 Oct 13;53(4):864-877.e5. doi: 10.1016/j.immuni.2020.07.026
- Liu L, Lin Q, Peng J, Fang J, Tan Z, Tang H, Kwan K, Nishiura K, Liang J, Kwok H, Du Z, Sun J, Liu K, Yuen KY, Wang H, Chen Z*. Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response. EBioMedicine. 2020 Sep 23; 60:103008.
- Chen Z. Editorial: The battle for survival between severe acute respiratory syndrome coronavirus 2 and human beings.Current Opinion HIV AIDS. 2020 Nov;15(6):325-327.
- Zhou D, Chan JF, Zhou B, Zhou R, Li S, Shan S, Liu L, Zhang AJ, Chen SJ, Chan CC, Xu H, Poon VK, Yuan S, Li C, Chik KK, Chan CC, Cao J, Chan CY, Kwan KY, Du Z, Lau TT, Zhang Q, Zhou J, To KK, Zhang L, Ho DD, Yuen KY, Chen Z*. Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies. Cell Host Microbe. 2021 Feb 25:S1931-3128(21)00098-6. doi: 10.1016/j.chom.2021.02.019.
- Wong YC, Liu W, Yim LY, Li X, Wang H, Yue M, Niu M, Cheng L, Ling L, Du Y, Chen SMY, Cheung KW, Wang H, Tang X, Tang J, Zhang H, Song Y, Chakrabarti LA, Chen Z*. Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination. PLoS Pathogens. 2021 Jun 14;17(6):e1009647.
- Wong YC, Lau SY, Wang To KK, Mok BWY, Li X, Wang P, Deng S, Woo KF, Du Z, Li C, Zhou J, Chan JFW, Yuen KY, Chen H, Chen Z*. Natural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients. Clinical Infectious Diseases. 2021 Jul 15;73(2):e437-e444.
- Zhang Q, Ju B, Ge J, Chan JF, Cheng L, Wang R, Huang W, Fang M, Chen P, Zhou B, Song S, Shan S, Yan B, Zhang S, Ge X, Yu J, Zhao J, Wang H, Liu L, Lv Q, Fu L, Shi X, Yuen KY, Liu L, Wang Y, Chen Z*, Zhang L*, Wang X*, Zhang Z*. Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2. Nature Communications. 2021 Jul 9;12(1):4210. doi: 10.1038/s41467-021-24514-w. PMID: 34244522; PMCID: PMC8270942.
- Niu M, Wong YC, Wang H, Li X, Chan CY, Zhang Q, Ling L, Cheng L, Wang R, Du Y, Yim LY, Jin X, Zhang H, Zhang L, Chen Z*. Tandem bispecific antibody prevents pathogenic SHIVSF162P3CN infection and disease progression. Cell Reports. 2021 Aug 24;36(8):109611.
- ZhouD, Zhou R, Chen Z*. Human neutralizing antibodies for SARS-CoV-2 prevention and immunotherapy. Immunotherapy Advances, Volume 2, Issue 1, 2022, ltab027, https://doi.org/10.1093/immadv/ltab027.
- Mo Y, To KK, Zhou R, Liu L, Cao T, Huang H, Du Z, Lim CYH, Yim LY, Luk TY, Chan JM, Chik TS, Lau DP, Tsang OT, Tam AR, Hung IF, Yuen KY, Chen Z*. Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients. Frontiers in Immunology. 2022 Jan 14;12:799896. doi: 10.3389/fimmu.2021.799896.
- Zhou R, Wang P, Wong YC, Xu H, Lau SY, Liu L, Mok BW, Peng Q, Liu N, Woo KF, Deng S, Tam RC, Huang H, Zhang AJ, Zhou D, Zhou B, Chan CY, Du Z, Yang D, Au KK, Yuen KY, Chen H, Chen Z*. Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models. EBioMedicine. 2022 Jan;75:103762.
- Zhou R, To KK, Peng Q, Chan MC, Huang H, Yang D, Lam HS, Chuang WM, Cai J, Liu N, Au KK, Tsang TY, Yuen KY, Chen Z*. Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses. Clinical and Translational Medicine. 2022 Jan 26;12;1;e720. Doi: 10.1002/ctm2.720
- Peng Q, Zhou R, Wang Y, Zhao M, Liu N, Li S, Huang H, Yang D, Au KK, Wang H, Man K, Yuen KY, Chen Z*. Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong. EBioMedicine. 2022 Mar 3;77:103904. doi: 10.1016/j.ebiom.2022.103904.
- Chen SMY, Wong YC, Yim LY, Zhang H, Wang H, Lui GCY, Li X, Tang X, Cheng L, Du Y, Peng Q, Wang J, Kwok HY, Huang H, Lau TT, Chan DPC, Wong BCK, Liu L, Chakrabarti LA, Lee SS, Chen Z*. Enhanced Cross-Reactive and Polyfunctional Effector-Memory T Cell Responses by ICVAX-a Human PD1-Based Bivalent HIV-1 Gag-p41 Mosaic DNA Vaccine. Journal of Virology. 2022 Mar 17:e0216121. doi: 10.1128/jvi.02161-21. Epub ahead of print. PMID: 35297660.
- Wang X, Chen X, Tan J, Yue S, Zhou R, Xu Y, Lin Y, Yang Y, Zhou Y, Deng K, Chen Z*, Ye L, Zhu Y. 35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope. Cell Host Microbe. 2022 Jun 8;30(6):887-895.e4.
- Zhou B, Zhou R, Tang B, Chan JF, Luo M, Peng Q, Yuan S, Liu H, Mok BW, Chen B, Wang P, Poon VK, Chu H, Chan CC, Tsang JO, Chan CC, Au KK, Man HO, Lu L, To KK, Chen H, Yuen KY, Dang S, Chen Z*. A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge. Nature Communications. 2022 Jun 23;13(1):3589. doi: 10.1038/s41467-022-31259-7. PMID: 35739114; PMCID: PMC9223271.
- Peng Q, Zhou R, Liu N, Wang H, Xu H, Zhao M, Yang D, Au KK, Huang HD, Liu L and Chen Z*. Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2. Cellular & Molecular Immunology. 2022 Nov;19(11):1302-1310. doi: 10.1038/s41423-022-00924-8. Epub 2022 Oct 12.
- Cao T, Liu L, To KK, Lim CY, Zhou R, Ming Y, Kwan KY, Yu S, Chan CY, Zhou B, Huang H, Mo Y, Du Z, Gong R, Yat LT, Hung IF, Tam AR, To WK, Leung WS, Chik TS, Tsang OT, Lin X, Song YQ, Yuen KY, Chen Z*. Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity. Clinical and Translational Medicine. 2022 Sep;12(9):e1025.
- Tan Z, Chiu MS, Yang X, Yue M, Cheung TT, Zhou D, Wang Y, Chan AW, Yan CW, Kwan KY, Wong YC, Li X, Zhou J, To KF, Zhu J, Lo CM, Cheng AS, Chan SL, Liu L, Song YQ, Man K, Chen Z*. Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients. Gut. 2022 Nov 30:gutjnl-2022-327133.
- Zhao F, Fung TY, Chen Z*, Wang H*, Cheung AKL*. Association of human cytomegalovirus in urine with end-organ diseases in stage 2/3 HIV-1-infected individuals. Journal of Clinical Virology. 2023 Jan;158:105351.
- Zhou R, Liu N, Li X, Peng Q, Yiu CK, Huang H, Yang D, Du Z, Kwok HY, Au KK, Cai JP, Fan-Ngai Hung I, Kai-Wang To K, Xu X, Yuen KY, Chen Z*. Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2: a population-based study in Hong Kong. The Lancet Regional Health – Western Pacific. 2023 Mar;32:100660.
- Luo M, Zhou B, Reddem ER, Tang B, Chen B, Zhou R, Liu H, Liu L, Katsamba PS, Au KK, Man HO, To KK, Yuen KY, Shapiro L, Dang S, Ho DD, Chen Z*. Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2. Emerging Microbes & Infections. 2023 Dec;12(1):2146538.
honours and awards
- Charles H. Revson/Norman and Rosita Winston Fellow 1998
- US NIH F32 Fellow 1998-2002
- Clinical Infectious Diseases Award for Outstanding Review 2010
- JAIDS Outstanding Reviewer Award 2015
- China New Development Award 2019 (Springer Nature)
- Faculty Knowledge Exchange Award 2018-19 (HKUMed)
- Knowledge Exchange Excellence Award 2019 (HKU)
- Outstanding Researcher Award 2020-21 (HKU)
- Outstanding Research Student Supervisor Award 2020-21 (HKU)
- Gold Medal in Inventions Geneva Evaluation 2021
- Faculty Outstanding Research Output Award 2021 (HKUMed)
- Most Picked Award – 2021 Chinese Scientists with Cell Press (Cell Press)
- Bronze Medal in Inventions Geneva Evaluation 2022
- Faculty Outstanding Research Output Award 2022 (HKUMed)
- Ranked by Clarivate Analytics as the top 1% worldwide by citations and one of the 38 HKU academics among Highly Cited Researchers 2022.
Reviewer for domestic and international grant applications:
- Hong Kong Health and Medical Fund (HMRF)
- National Natural Science Foundation of China
- Science, Technology and Innovation Commission of Shenzhen Municipality
- American Foundation for AIDS Research (amFAR)
- The Bill & Melinda Gates Foundation
- Netherlands Organization for Scientific Research
- British St Stephen’s AIDS Trust
- Israel Science Foundation (ISF)
EDITORSHIP
- Immunotherapy Advances, Founding Editorial Board Member, since 2020; Publisher: Oxford University Press, invited by British Society for Immunology
- AIDS: Member of Editorial Board, since Jan 2017; Publisher: Lippincott Williams & Wilkins, USA
- Journal of Acquired Immune Deficiency Syndromes(JAIDS); Member of Editorial Board, since Jan 2010; Publisher: Lippincott Williams & Wilkins, USA
- Journal of Neuroimmune Pharmacology (JNIP); the peer-reviewed journal of the Society on NeuroImmune Pharmacology. Publisher: Springer
- Journal of Leukocyte Biology, Guest editor, 2020
- Current Opinion in HIV and AIDS,Invited guest editor for the November Issue 2020 on COVID-19, together with the invited Editorial Introduction.
- Journal of Medical Primatology, Member of Editorial Board, since 2008; Publisher: Blackwell-Wiley InterScience
- PLoS ONE, Academic Editor and Member of Editorial Board since 2010; Publisher: Public Library of Science, USA
- Journal of Antivirals and Antiretrovirals (Editor/Member of Editorial Board, since 2009); Publisher: OMICS Publishing Group
- Faculty Member of F1000, F1000 Faculty comprises the world’s leading researchers across all of biology and medicine
GRANT RECORD
Fellowship, Awards and Grants in the USA
1998-1999 Fellowship award from the Charles H. Revson/Norman and Rosita Winston Foundation,The Rockefeller University. Role: Principal Investigator
1998-2002 Grant funded by National Institutes of Health (NIH/NIAID, 1F32AI 10256), Characterization of a CCR2-tropic recombinant simian immunodeficiency virus; Role: Principal Investigator
2000-2001 Grant funded by the American Foundation for AIDS Research (amFAR, 02663-27-RGM); Development of a Novel SHIV/Macaque Model for Microbicide Testing, US$120,000; Role: Principal Investigator
2005-2009 Grant from National Institutes of Health, USA; (NIH RO1 HL080211-01); US$2.4 million; A Novel Model for the Study of Lung Pathogenesis of SARS; Role: Principal Investigator
External Grants Received from the USA for Research at HKU (HK$7.3 million to my group at HKU)
2007-2009 Grant from National Institutes of Health, USA; (NIH 5 R01 HL080211-03); US$2.4 million; A Novel Model for the Study of Lung Pathogenesis of SARS; Role: Principal Investigator; (US$292,450 to my HKU Lab)
2007-2011 Grant from National Institutes of Health, USA; (NIH 3 R01 DA020419-02S1); Cannabinoid effects on HIV/AIDS; US$320,000, Role: Co-Principal Investigator
2008-2009 Grant BMGF 52117, Bill & Melinda Gates Foundation; Preventing HIV-1 infection using a novel vaccine immunogen; US$100,000; Role: Principal Investigator
2017-2021 Grant from Bill & Melinda Gates Foundation for the National Institutes of Health (AR170035), USA; Structure-Based Vaccine Design against HIV-1, US$220,000; Role: Co-Principal Investigator
External Grant Received from the UK for Research at HKU (HK$3.18 million to my group at HKU)
2020 – 2022 Grant from Wellcome Trust (the Funder) for project entitled “A comprehensive study of immunopathogenesis of SARS-CoV-2 infection”, £315,689.63 to my group at HKU, Role: Co-Principal Investigator
External Grant Received from the Coalition for Epidemic Preparedness Innovations (CEPI) for COVID-19 Vaccine Research at HKU (HK$48.36 million)
2020 – 2020 Phase I US$600,000, Role: Co-Principal Investigator
2020 – 2022 Phase II US$5,600,000, Role: Co-Principal Investigator
External Awards and Grants Received from Australia for Research at HKU (HK$590300 to my group)
2020 – 2022 Grant from Australian MRFF 2020 COVID-19 Vaccine Candidate Grant Opportunity for project entitled “A safe, effective, and rapidly tuneable SARS-CoV-2 vaccine”, A$100K. Role: Co-Investigator
External Awards and Grants Received in Hong Kong as PI (HK$110 million to my group)
2008-2009 Grant RGC-GRF 762208M, HKSAR;Mucosal vaccine against HIV-1 infection; HK$517,190; Role: Principal Investigator
2008-2009 Understanding the Ongoing HIV Epidemic in Yunnan China; Supported by China AIDS Initiative (Hong Kong Committee); HK$196,000; Role: Principal Investigator
2009-2012 Grant RGC-GRF 762209M, HKSAR; Role of the PD-1/PD-L pathway in AIDS vaccine design; HK$944,700; Role: Principal Investigator
2010-2012 Grant RFCID 09080772, HKSAR; Characterization of novel anti-HIV/TB natural product analogues, HK$800,000; Role: Principal Investigator
2011-2013 AIDS Trust Fund (ATF) MSS 183 R, HKSAR; Establishment of a rapid, high-throughput, cost-effective HIV-1 drug resistance testing system; HK$1,573,000; Role: Principal Investigator
2011-2013 Pneumoconiosis Compensation Fund Board (PCFB), HKSAR; A Novel Vaccine for Mesothelioma Immunotherapy and Prevention; HK$1,718,000; Role: Principal Investigator
2011-2013 Grant RFCID 11101022, HKSAR, A Novel Vaccine for Tuberculosis Prevention; HK$994,560; Role: Principal Investigator
2012-2014 Grant RGC-GRF 762811M, HKSAR; A Promising Mucosal Prime and Intramuscular Boost AIDS Vaccine Regimen; HK$950,000; Role: Principal Investigator
2012-2015 Grant RGC-NSFC N_HKU 709/11, HKSAR; HIV prevention using gene-encoded neutralizing antibodies; HK$892,290; Role: Principal Investigator
2013-2015 Grant Information Technology Fund (ITF) GHX/013/11SZ, HK$682,642. Phenotypic Assay for HIV drug resistance; Role: Principal Investigator
2013-2016 Grant RGC-GRF 762712, HKSAR; Mechanism of soluble PD-1 based vaccine in amplifying antiviral CD8+ T-cell immunity; HK$1,248,250; Role: Principal Investigator
2014-2016 Grant ITF ITS/194/13, HKSAR; A New Therapeutic Vaccine for HIV/AIDS; HK$1,391,400; Role: Principal Investigator
2014-2017 Grant RGC-CRF HKU5/CRF/13G, HKSAR; Mechanism of potentiating HIV antigen-specific CD8+ T cells; HK$7,984,380; Role: Project Coordinator
2014-2017 Grant ATF MSS 227R, HKSAR; The level of GFAP as a specific biomarker of neuroAIDS among Chinese patients; HK$1,904,800; Role: Principal Investigator
2015-2016 Grant PCFB, HKSAR; Induction of Mesothelioma-Specific CD8+ T cells Response for Immunotherapy and Prevention; HK$1,361,090; Role: Principal Investigator
2015-2019 Grant RGC-ANR A-HKU709/14, HKSAR; A novel DNA-based vaccination strategy to mimic Gag specific responses found in HIV Elite Controllers; HK$2,550,110; Role: Principal Investigator
2015-2017 Grant RGC-GRF 17103514, HKSAR; Role of a newly identified PD-1 isoform in modulating immune responses; HK$1,144,050; Role: Principal Investigator
2015-2017 Grant HMRF 14130582, HKSAR; Role of Delta 42PD-1 in HIV Infection; HK$999,980; Role: Principal Investigator
2016-2018 Grant RGC-GRF 17122915, HKSAR; Role of PD-1 Based Vaccine-Elicited CD8+ T Lymphocytes in Modulating MDSC-associated Immunosuppression; HK$977,450; Role: Principal Investigator
2017-2018 Grant PCFB, HKSAR; Induction of Mesothelioma-Specific CD8+ T cells Response for Immunotherapy and Prevention; HK$1,499,980; Role: Principal Investigator
2018-2019 Grant ITF ITS/170/17, HKSAR; A Novel Therapeutic AAV-vectored Bi-Specific Neutralizing Antibody against HIV/AIDS; HK$1,399,550; Role: Principal Investigator
2018-2019 Grant ITF UIM/314, HKSAR; A novel PD1-based vaccine for HIV/AIDS Immunotherapy; HK$11,998,000; Role: Principal Investigator
2018-2019 Grant PCFB, HKSAR; Enhancing immunotherapeutic efficacy of mesothelioma by overcoming MDSC-mediated immunosuppression; HK$1,414,330; Role: Principal Investigator
2018-2021 Industry Contract Research, A Humanized anti-d42PD1 antibody against human inflammatory disease and cancer, HK$4,000,000; Role: Principal Investigator
2019-2021 Grant RGC-GRF 17115818, HKSAR; Role of Δ42PD-1 in Human Dendritic Cells during HIV-1 Infection; HK$971,900; Role: Principal Investigator
2019-2021 Grant HMRF 18170762, HKSAR; HIV-1 mucosal prevention and immunotherapy by engineered tandem bi-specific IgA; HK$1,499,940; Role: Principal Investigator
2019-2023 Grant RGC-TRS T11-706/18-N, HKSAR; Potentiating Host Immunity for HIV-1 Functional Cure; HK$47.128 million; Role: Project Co-ordinator
2020-2022 Grant RGC-GRF 17104919, HKSAR; Mechanism of a Δ42PD-1-specific humanized antibody huCH101 in treating HIV/AIDS; HK$1,115,990; Role: Principal Investigator
2021-2024 Grant RGC-CRF C7156-20G, HKSAR; Mechanism of Immune Control against COVID-19; HK$8,979,578; Role: Project Coordinator
2022-2025 Grant RGC-GRF 17117422, HKSAR; Mechanism of vaccine-induced mucosal immune responses against SARS-CoV-2 infection; HK$1,179,038; Role: Principal Investigator
External Awards and Grants Received in Hong Kong as Co-PI (HK$69 million to my group at HKU)
2015-2018 Grant RGC-CRF C7038-14G, HKSAR; Investigation of effects and molecular mechanisms of FGFR2-positive cancer-associate fibroblasts on tumor microenvironment in esophageal squamous cell carcinoma; HK$800,000; Role: Co-Principal Investigator
2017-2020 Grant from Sanming Project (AR160087); Study on AIDS Vaccine and Immunotherapy; HK$2,230,000; Role: Project Leader
2019-2022 Grant RGC-CRF C4045-18W, HKSAR; Deciphering Enhancer Regulation of Tumor Immune Evasion to Develop New Combination Immunotherapies; HK$1,200,000; Role: Co-Principal Investigator
2020-2022 HMRF Commissioned Research (COVID190123); “Clinical study of flu-based and PD1-based vaccines for the SARS-CoV-2”; HK$10 million (from the total of HK$20,337,934; Role: Co-Principal investigator
2020-2025 Grant RGC-TRS T12-703/19-R, HKSAR; Fighting Disease Recurrence and Promoting Tissue Repair after Liver Transplantation: Translating Basic Discoveries to Clinical Excellence; HK$6,000,000; Role: Co-Principal Investigator
2020-2025 InnoHK “Centre for Virology, Vaccinology and Therapeutics”, HKSAR; HK$47 million; Role: Project Co-Principal Investigator (from the total budget of about HK$400 million).
2021-2024 Grant RGC-CRF C1134-20G, HKSAR; A novel vaccination strategy: using a microrobot platform for DNA vaccine delivery and antigen presentation; HK$1,000,000; Role: Co-Principal Investigator
2022-2026 Grant RGC-TRS T11-709/21-N, HKSAR; Ecology, Molecular Virology and Pathogenesis of SARS-CoV-2: From Bedside to Bench and Back; HK$1,000,000; Role: Co-Principal Investigator
External Awards and Grants Received for Research in Mainland China (RMB¥24.9 million)
2006-2010 Chinese 973 Research Program on HIV/AIDS; RMB¥600,000; Role: Project 8 Leader
2008-2010 Grant from the China Ministry of Health; Novel AIDS mucosal vaccine (2008ZX10001-011); RMB ¥2,800,000; Role: Project Leader
2008-2010 Grant from the China Ministry of Health; (2008ZX10001-015); Microbicide against HIV; RMB ¥1,500,000; Role: Project Leader
2012-2015 Grant from the China Ministry of Health; Novel AIDS mucosal vaccine (China’s Major Project of the National Science & Technology 2012ZX10001-009); RMB ¥6,100,000; Role: Project 1 Leader
2013-2016 Grant from the China Ministry of Health; Novel Anti-HIV Antibody for Prevention (China’s Major Project of the National Science & Technology 2017ZX10201101-004); RMB ¥3,000,000; Role: Project 4 Leader
2020-2022 Grant from the Shenzhen Government at HKU SZH; PD1-based COVID-19 vaccine (ICCOV); JSGG20200225151410198; RMB ¥8,000,000; Role: Principal Investigator
2020-2022 Sub-grant from the Ministry of Science and Technology at HKU SZH; Mechanism of antibody-enhanced SARS-CoV-2 infection; 2020YFC0860600; RMB ¥500,000; Role: Co-Investigator
2022-2023 Grant from the Shenzhen Government at HKU SZH; Development portable Raman instrument for COVID disease detection; JSGG220220606141800002; RMB ¥2,400,000; Role: Co-Investigator
professional recognition
Member, Advisory Council on AIDS, Department of Health, HKSAR Government (2008 – 2014)
Member, Executive Committee, China AIDS Vaccine Initiative (2008 – present)
Member, Expert Committee, China AIDS Vaccine Network (2008 – present)
American Association of Immunologists
Member, American Society for Microbiology
Council Member, American Society on NeuroImmune Pharmacology (SNIP)Editorial Service for Peer-reviewed International Journals
Member, Editorial Board, JAIDS (2010 – present)
Member, Editorial Board, Journal of Antivirals and Antiretrovirals (2009 – present)
Member, Editorial Board, Journal of Medical Primatology (2008 – present)
Member, Editorial Board, Virologica Sinica (2007 – present)
Member of Editorial Board and Academic Editor, PLoS ONE (2010 – present)