Zhang, Weiping
Education
PhD, Iowa State University, Ames, Iowa
Links
Research Biography
The Zhang laboratory studies the disease mechanism of enteric bacteria and develops vaccines against diarrheal disease, with the main focus on enterotoxigenic Escherichia coli (ETEC), Shigella, and cholera. ETEC and Shigella are the leading cause of children’s diarrhea and travelers’ diarrhea and the significant risk of antibiotic resistance, and cholera remains a major threat to public health. ETEC is also a predominant cause of diarrhea in young animals, particularly newly weaned pigs. The development of effective vaccines against these enteric bacteria is the top priority for the World Health Organization (WHO), the US National Institutes of Health (NIH), and many other public health institutes.
Applying isogenic strains and animal models, the research team determines the significance of individual virulence factors and identifies virulence determinants, then targets virulence determinants as antigens for the development of precision vaccines.
Collaborating with world-class scientists, the group combines the epitope vaccine concept and the structure vaccine concept and has developed a novel epitope- and structure-based vaccinology platform to develop protein-based safe and cross-protective vaccines (multivalent vaccines and combination vaccines) against heterogeneous strains or different diseases.
The laboratory develops different animal models to study disease mechanisms and to evaluate vaccine pre-clinical efficacy. Animal models routinely used in the laboratory include pig (conventional as well as germ-free), mouse, and rabbit (adult model, pregnant model, and infant passive or active model).
His research program has been well-funded by NIH, USDA-NIFA, and private funding agencies including PATH.
The laboratory currently accepts applications for postdoc research associates and PhD-level graduate students.
Grants
NIH R01AI177144-01 Development of MecVax, a cross-protective subunit vaccine for ETEC. $5,769,225. 6/1/2023 – 5/30/2028.
NIH R01AI175214-01 A cross-protective multivalent vaccine for Shigella and ETEC. $3,921,648 ($1,995,056). 3/6/2023 – 2/29/2028.
NIH R01AI121067-01A1 A broadly protective subunit vaccine against enterotoxigenic Escherichia coli $2,110,587. 9/1/16- 4/30/23.
NIAID HHSN272201800011I-0-759302000003-1 (NIH Pre-Clinical Service) Development and Manufacture of Toxoid Fusion: Master Cell Banks. $1,209,261. 5/15/2018 – 5/14/2028.
USDA/NIFA 2017-67015-26632 A broadly protective vaccine against porcine post-weaning diarrhea (PWD). $457,711. 5/15/2020 - 5/14/2025.
Selected Publications
- Upadhyay I, SM Parvej, Y. Shen, S Li, KL Lauder, C. Zhang, W. Zhang*. 2023. Protein-based vaccine candidate MecVax broadly protects against intestinal colonization of ETEC strains expressing different adhesins (CS1 – CS6) in a rabbit model. Infect Immun 91(11):e0027223.
- Li S, S Anvari, G Ptacek, I Upadhyay, RW Kaminski, DA Sack, W Zhang*. 2023. A broadly immunogenic polyvalent Shigella multiepitope fusion antigen (MEFA) protein protects against S. sonnei and S. flexneri lethal pulmonary challenges in mice. Infect Immun 91(11):e0031623.
- Upadhyay I, S Li, H Seo, DA Sack, W Zhang*. 2022. A polyvalent protein antigen and rabbit colonization and infant passive protection models for a multivalent cholera vaccine. Proc Natl Acad Sci USA, 119(50):e2202938119.
- Upadhyay I, KL Lauder, S Li, G Ptacek, W Zhang*. 2022. Intramuscularly administered enterotocigenic Escherichia coli (ETEC) vaccine candidate MecVax prevented H10407 intestinal colonization in an adult rabbit colonization model. Microbiol Spect 10(4):e0147322.
- Li, S, X Han, I Upadhyay, W. Zhang*. 2022. Characterization of functional B-cell epitopes at the amino terminus of Shigella invasion plasmid antigen B (IpaB). Appl Environ Microbiol 88(15):e0038422.
- Seo H, Q Duan, I Upadhyay, W Zhang*. 2022. Evaluation of multivalent enterotoxigenic E. coli vaccine candidate MecVax antigen dose-dependent effect in a murine model. Appl Environ Microbiol 88(17):e0095922.
- Kyle D. Brumfield, Hyesuk Seo, Nne Idegwu, Chad Artman, Weiping Zhang, David Sack, Julius Goepp. 2022. Feasibility of Avian Antibodies as Prophylaxis Against Diarrheal Illness. Front Immun 13:e1011200.
- Garcia YC, H Seo, DA Sack, W. Zhang*. 2022. Intradermally administered enterotoxigenic E. coli vaccine candidate MecVax induces functional serum IgG antibodies against seven adhesins (CFA/I, CS1-CS6) and both toxins (STa, LT). Appl Environ Microbiol, 88(4):e0213921.
- Jones R, H Seo, W Zhang, DA Sack. 2022. A multi-epitope fusion antigen (MEFA) candidate vaccine for ETEC is protective against strain B7A colonization in a rabbit model. PLOS Negl Trop Dis, 16(2):e0010177.
- Li S, KH Lee, W Zhang*. 2022. Multiepitope fusion antigen: MEFA, an epitope- and structure-based vaccinology platform for multivalent vaccine development. Methods Mol Biol 2412:151-169.
- Seo H, C Garcia, XS Ruan, QD Duan, DA Sack, W Zhang*. 2021. MecVax, a novel structure- and epitope-based multivalent enterotoxigenic E. coli vaccine for broad protection against ETEC-associated diarrhea. Infect Immun 89(7):e00106-21 (Spotlight Selection/Vaccines).
- Cox E, M Aloulou, J Fleckenstein, C Schäffer, Å Sjöling, S Schuller, K Hanevik, B Devriendt, W Zhang, A M Svennerholm, E Dudley. 2020. The intriguing interaction of Escherichia coli with the host environment and innovative strategies to interfere with colonization: A summary of the 2019 E. coli and the Mucosal Immune System meeting. Appl. Environ. Microbiol. 86(24):e2085-20.
- Seo H, QD Duan, W Zhang*. 2020. Vaccines against gastroenteritis, current progress and challenges. Gut Microbes 11(6):1487-1517.
- Duan QD, S Pang, W Wu, B Jiang, W Zhang, S Liu, X Wang, Z Pan, G Zhu. 2020. A multivalent vaccine candidate targeting enterotoxigenic Escherichia coli fimbriae for broadly protecting against porcine post-weaning diarrhea. Vet. Res. 51(1):93.
- Lu T, RA Rodney, W. Zhang*. 2020. Immunogenicity characterization of a fimbria-toxin multiepitope fusion antigen (MEFA) of enterotoxigenic Escherichia coli (ETEC) causing post-weaning diarrhea (PWD) in pigs. Appl. Environ. Microbiol. 86(24): AEM00274-20.
- Duan QD, W Wu, Z Pan, S Pang, W Zhang, G Zhu*. 2020. Co-administered two enterotoxigenic Escherichia coli (ETEC) fimbriae MEFA (multiepitope fusion antigen) induce neutralizing antibodies against five ETEC fimbriae: F4, F5, F6, F18 and F41. Appl. Environ. Microbiol. 86(24):AEM.00217-20.
- Ou, BM; B Jiang, J Duo; Y Yang, MY Zhang, D Zhang, HZ Zhao, MX Xu, HL Song, WW Wu, ML Chen, T Lu, JC Huang, H Seo, C Garcia, WL Zheng, WY Guo, YH Lu, S Yang, R Kaushik, XC Li, W Zhang*, GQ Zhu*. 2020. Engineered recombinant Escherichia coli probiotic strains integrated with F4 and F18 fimbriae cluster genes in the chromosome and their assessment of immunogenic efficacy in vivo. ACS Synth Biol. 9(2):412-426.
- Seo H, W Zhang*. 2020. Development of effective vaccines for enterotoxigenic Escherichia coli. Lancet Infect. Dis. 20(2):150-152.
- Seo H, T. Lu, S. Mani, AL Bourgeois, R Walker, DA Sack, W. Zhang*. 2020. Adjuvant dose effect of enterotoxigenic Escherichia coli (ETEC) double mutant heat-labile toxin (dmLT) on upimmunoregulating CFA/I/II/IV MEFA for antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6). Hum Vaccin Immunother 16(2):419-425.
- Duan QD, P Xia, RM Nandre, W. Zhang*, GQ Zhu*. 2019. A review of newly identified functions associated with heat-labile toxin of enterotoxigenic Escherichia coli. Front. Cell. Infect. Microbiol. 9: e00292.
- Seo H, MR Nandre, J. Nietfeld, Z Chen, J. Huang, QD Duan, W. Zhang*. 2019. Antibodies derived from enterotoxigenic Escherichia coli (ETEC) adhesin major structural subunit antigen and minor tip subunit antigen equivalently inhibited bacteria in vitro adherence. PLoS ONE 14(5):e0216076.
- Lu T, R. Moxley, W. Zhang*. 2019. Mapping the neutralizing epitopes of enterotoxigenic Escherichia coli (ETEC) K88 (F4) fimbrial adhesin and major subunit FaeG. Appl. Environ. Microbiol. 85(11):e00329.
- Lu T, H. Seo, RA Rodney, W. Zhang*. 2019. Mapping the neutralizing epitopes of F18 fimbrial adhesin subunit FedF of enterotoxigenic Escherichia coli (ETEC). Vet. Microbiol. 230:171-177.
- Seo H, T. Lu, RM Nandre, Q. Duan, W. Zhang*. 2019. Immunogenicity characterization of genetically fused or chemically conjugated enterotoxigenic Escherichia coli (ETEC) heat-stable toxin (STa) toxoids in mice and pigs. FEMS Microbiology Lett. 366(4):fnz037.
- Huang J, QD Duan, and W Zhang*. 2018. The significance of enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) enzymatic subunit epitopes in LT enterotoxicity and immunogenicity. Appl. Environ. Microbiol. 84(15):e00849-18.
- Duan QD, T Lu, C Garcia, C Yanez, RM Nandre, DA Sack, W Zhang*. 2018. Co-administered tag-less toxoid fusion 3xSTaN12S-mnLTR192G/L211A and CFA/I/II/IV MEFA (multiepitope fusion antigen) induce neutralizing antibodies to 7 adhesins (CFA/I, CS1-CS6) and both enterotoxins (LT, STa) of enterotoxigenic Escherichia coli (ETEC). Frontiers in Microbiology, 9:e1198.
- Nandre R, XS Ruan, T Lu, DA Sack, W Zhang*. 2018. Enterotoxigenic Escherichia coli (ETEC) adhesin-toxoid MEFA (multiepitope fusion antigen) CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A derived antibodies inhibit adherence of seven adhesins (CFA/I, CFA/II & CFA/IV), neutralize enterotoxicity of both toxins (LT & STa), and protect piglets against diarrhea. Infect. Immun. 86(3):e00550-17.
- Duan QD, JC Huang, N Xiao, H Seo, W Zhang*. 2018. Neutralizing anti-STa antibodies derived from enterotoxigenic Escherichia coli (ETEC) toxoid fusions with heat-stable toxin (STa) mutant STaN12S, STaL9A/N12S or STaN12S/A14T show little cross-reactivity with guanylin or uroguanylin. Appl. Environ. Microbiol. 84(2): e01737-17).
* indicates the corresponding author