AIDS Vaccine and Pathogenesis

Zhiwei Chen, PhD, DVM
Associate Professor and Director, AIDS Institute
DVM (Northwestern Agricultural University); MSc (New Mexico State University); PhD (New York University)

Contact          
Email: zchenai@hku.hk
Tel: (852) 2819 9831; Fax: 2817 7805
Office: Room 44, 5/F, Laboratory Block, 21 Sassoon Road, Pokfulam

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 a multivalent SIV and HIV vaccine using a live modified vaccinia Tiantan (MVTT) strain.  For this purpose, 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 strong cell-mediated and antibody responses to all three SIV gene products, which conferred significant protection against SIVmac239 challenge.  Interestingly, mucosal delivery of this vaccine has induced much stronger SIV-specific immune responses in animals.  As a preventive means, I will further develop, optimize, and eventually test MVTT-based vaccine in humans in the near future.  For the assessment of the vaccine efficacy, I am also playing an active role in a molecular epidemiology study of HIV 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 system, we are constructing vaccines to prevent SARS-CoV, Influenza and HCV infections.

Selected publications

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.

Marx PA and Chen Z.  The function of simian chemokine receptors in the replication of SIV.  Seminars in Immunology (Review article) 10:215-223, 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).  JAIDS 30:133-145, 2002.

Su B, Liu L, Wang F, Gui X, Zhao M, Tien P, Zhang L and Chen Z*.  Human immunodeficiency virus type 1 subtype B’ dictates the current AIDS epidemic among paid blood donors in Henan and Hubei Provinces of China.  AIDS. 21;17(17):2515-20.  2003.

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)

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 Med.  Nov;3(11):e443. 2006.

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*.  Resistance of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus.  Journal of Virology.  May;81(9):4694-700. Epub 2007 Feb 21. 2007.

Ma T, Liu L, Xue H, Li L, Han C, Wang L, Chen Z, Liu G. Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents.  Journal of Medicinal Chemistry.  Mar 13;51(5):1432-46. 2008.

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.  Apr 1;47(4):412-21. 2008.

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.  Nov 10; 381(1):89-97. Epub 2008 Sep 17. 2008.

Lu L, Jia MH, Ma YL, Chen Z, Ho D, and Zhang L.  Changing landscape of HIV-1 infection in Yunnan, China.  Nature.  Oct 2. 455:609-11, 2008.

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.

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 modified vaccinia Tian Tan (MVTT) as a mucosal vaccination vehicle.  PLoS ONE.  4(1):e4180. 2009; Epub 2009 Jan 13.

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. 2009 Dec 30. [Epub ahead of print].

Wang H, Zhuang K, Liu. L, Tang Z, Tang J, Tien P, Zhang L, and Chen Z*. Acute infection of Chinese macaques with an CCR5-tropic SHIV carrying a primary HIV-1 subtype B' envelope.  JAIDS.  2010 Jan 4. [Epub ahead of print]

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), pp 1397–1401. 2010.

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

Liu Li, Qiang Wei, Xavier Alvarez, Haibo Wang, Yanhua Du, Hua Zhu, Hong Jiang, Jingying Zhou, Pokman Lam, Jenny Ng, Linqi Zhang, Andrew Lackner, Chuan Qin, and 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, Apr; 85(8):4024-30.

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. (*corresponding author) (IF: 1.225)

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) (IF: 4.911).

Zhang Q, Zhang X, Wu H, Seto D, Zhang H-J, Chen Z, Wan CS, Zheng BJ. Parental LTRs Are Important in a Construct of a Stable and Efficient Replication-Competent Infectious Molecular Clone of HIV-1 CRF08_BC. PLoS ONE 2012. 7(2): e31233. doi:10.1371/journal.pone.0031233 (IF: 4.411).

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. J of AIDS. 2012 Jul 1; 60(3): 328-35. (*corresponding author) (IF: 4.425).

Zhou F, Wang G, Buchy P, Cai Z, Chen H, Chen Z, Cheng G, Wan XF, Deubel V, Zhou P. A triclade DNA vaccine designed on the basis of a comprehensive serologic study elicits neutralizing antibody responses against all clades and subclades of highly pathogenic avian influenza H5N1 viruses. Journal of Virology. 2012 Jun; 86(12): 6970-8.

Qiu M, Wang Q, Chu Y, Yuan Z, Song HY, Chen Z*, and Wu Z* Lignosulfonic acid shows potent antiretroviral activity - potential as a microbicide candidate for the prevention of HIV-1 sexual transmission. PLoS One. 2012, 7(4): e35906. doi:10.1371/journal.pone.0035906 (*co-corresponding author).

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. (IF: 4.8) (*corresponding author)

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

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. Online published. (IF: 5.402) (Shared first author and *corresponding author)

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. In press. (IF: 14.1). (*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. In the press. (IF: 6.87). (*corresponding author)