Zhiwei Chen, PhD, DVM

 

Director, AIDS Institute
Professor, Department of Microbiology, LKS Faculty of Medicine,
The University of Hong Kong

DVM (Northwestern Agricultural University);
MSc (New Mexico State University);
PhD (New York University


Contact

Email: zchenai@hku.hk

Tel: (852) 3917 9831; Fax: 2817 7805
Office: Room 44, 5/F, Laboratory Block, 21 Sassoon Road, Pokfulam

 

ORCID : https://orcid.org/0000-0002-4511-2888

 

 

Professional Recognitions

 

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)

 


 

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.

 


 

Selected Publications

1. 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.


2. 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.


3. 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.


4. 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.


5. Marx PA and Chen Z. The function of simian chemokine receptors in the replication of SIV. Seminars in Immunology (Invited review article) 10:215-223, 1998.


6. 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.


7. 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.


8. 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). JAIDS. 30:133-145, 2002.


9. Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie GJ, Lin G, Granelli-Piperno A, Doms RW, Rice CM, McKeating JA. Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. Journal of Virology. Apr;77(7):4070-80, 2003.


10. 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. (*corresponding author).


11. Wu Z, Chen Z, Phillips DM. Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ Cells: implications for mechanisms of sexual transmission. J Infect Dis. 188(10):1473-82. 2003.


12. Zhang L, Chen Z, Cao Y, Yu J, Li G, Yu W, Yin N, Mei S, Li L, Balfe P, He T, Ba L, Zhang F, Lin HH, Yuen MF, Lai CL, Ho DD. Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china. Journal of Virology. 78(24):13591-9. 2004. (Shared the first author).


13. 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. (*corresponding author)


14. 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. (*corresponding author)


15. 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. (*corresponding author).


16. 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. (*corresponding author)


17. 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. Epub 2007 Feb 21. (*corresponding author)


18. Zhu W, Fang Q, Liu L, Wang H, Zhou J, Yu W, Tien P, Zhang L, Chen Z*. The attenuation of vaccinia Tian Tan strain by the removal of the viral M1L-K2L genes. Journal of Virological Methods. 2007 Sep;144(1-2):17-26. Epub 2007 Apr 24. (*corresponding author)


19. 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. Appl Microbiol Biotechnol. 2007 Oct;76(5):1131-6. Epub 2007 Jun 21. (*corresponding author)


20. 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’. JAIDS. 2008 Apr 1;47(4):412-21.


21. Huang Y, Chen Z, Zhang W, Song Y, Zhao X, Gardiner DF and Ho DD. Design, Construction, and Characterization of a Dual-Promoter Multigenic DNA Vaccine Directed against an HIV-1 Subtype C/B’ Recombinant. JAIDS. 2008 Apr 1;47(4):403-11. (IF: 4.425; Cited: 14.)


22. Chen YX, Liu L, Wei Q, Zhu H, Jiang H, Tu XM, Qin C and Chen Z*. Angiotensin Converting Enzyme Two of Chinese Rhesus Macaques Determines Entry Efficiency of Severe Acute Respiratory Syndrome Coronavirus. Virology. 2008 Nov 10;381(1):89-97. (*corresponding author)


23. Lu L, Jia M, Ma Y, Yang L, Chen Z, Ho DD, Jiang Y, Zhang L. The Changing Face of HIV in China. Nature. Oct 2. 455:609-11, 2008.


24. 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. JAIDS. Jan 1; 50(1): 1-8. 2009.


25. 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. (*corresponding author)


26. Cheng S, LI J, Lin B, Lee D, Liu L, Chen Z, Lau A. HIV-1 trans-activator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNgamma signaling. Blood. 2009 May 21;113(21):5192-201.


27. Vasan S, Schlesinger SJ, Chen Z, Hurley A, Lombardo A, Than S, Adesanya P, Bunce C, Boaz M, Boyle R, Sayeed E, Clark L, Dugin D, Boente-Carrera M, Schmidt C, Fang Q, LeiBa, Huang Y, Zaharatos GJ, Gardiner DF, Caskey M, Seamons L, Ho M, Dally L, Smith C, Cox J, Gill D, Gilmour J, Keefer MC, Fast P, Ho DD. Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-based Clade C/B’ HIV-1 Candidate Vaccine. PLoS ONE. 2010 Jan; 5(1):e8816.


28. 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. (*corresponding author)


29. 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. (*corresponding author)


30. Tang X and Chen Z*. The development of an AIDS mucosal vaccine. Viruses. 2010, 2(1), 283-297. (Invited review article) (*corresponding author)


31. 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. JAIDS. Mar 1:53(3):285-291. 2010. (*corresponding author)


32. 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. J Med Virol. 2010 May;82(5):727-34. (*corresponding author)


33. 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. (*corresponding author)


34. 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. (*corresponding author)


35. 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. JAIDS. 2012 Jul 1; 60(3): 328-35. (*corresponding author)


36. 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. J Biol Chem. 2012 May 11;287(20):16499-509. (*corresponding author)


37. Kang Y, Guo J and Chen Z*. Closing the door to human immunodeficiency virus. Protein & Cell. 2013 4(2):86-102. (Invited Review Article).


38. 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).


39. Zhou J, Cheung AKL, Tan Z, Wang H, Kang Y, Du Y, Lu X, Liu L, Yuen KY and Chen Z*. sPD1-based DNA vaccine amplifies HIV-1 CD8+ T cells in mice. Journal of Clinical Investigation. 2013 Jun 3;123(6):2629-42. (*corresponding author)


40. 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. Mol Ther. 2013 Jul;21(7):1445-55. (*corresponding author)


41. Peng Q, Wang H, Wang HB, Li X, Lu X, Zhou B, and Chen Z* Imbalances of gut-homing CD4+ T cell subsets in HIV-1 infected Chinese patients. JAIDS. 2013 Sep 1;64(1):25-31. (*corresponding author)


42. 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. (*corresponding author)


43. Tan Z, Zhou J, Cheung AKL, Yu Z, Cheung KW, Liang JG, Wang HB, Lee BK, Man K, Liu L, Yuen KY and Chen Z* Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. Cancer Research. 2014. in press. (*corresponding author)

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