PhD, Iowa State University, Ames, Iowa
Trained as a molecular biologist, a microbiologist, and a vaccinologist, Dr. Weiping Zhang currently focuses on diarrheal disease pathobiology research and vaccine development, mainly of enterotoxigenic Escherichia coli (ETEC). By studying molecular pathogenesis of individual enterotoxins produced by ETEC using a gnotobiotic (germ-free) piglet model, he determined virulence significance of each toxin in ETEC diarrheal disease and developed a pig challenge model for human ETEC vaccine development.
By applying toxoids as safe vaccine antigens and a genetic fusion strategy to enhance immunogenicity of small-sized poorly immunogenic toxin peptides, his laboratory produced safe toxoid fusion antigens that induce protective antibodies against the key ETEC enterotoxins, an achievement hailed as a major breakthrough in ETEC vaccine development.
Recently, his research team has developed structure- and epitope-based MEFA (multiepitope fusion antigen) technology for developing broadly protective multivalent vaccines against porcine post-weaning diarrhea (PWD), children’s diarrhea, and travelers’ diarrhea.
Like many other pathogens, ETEC strains produce immunologically heterogeneous virulence factors, a major challenge in vaccine development. Applying the MEFA technology and structural vaccinology, his laboratory has created a single antigen carrying antigenic elements (epitopes) of multiple heterogeneous virulence factors to induce broadly protective antibodies against the most important ETEC strains, accelerating the development of truly effective ETEC vaccines.
Additionally, his team collaborates with other prominent vaccine development programs to develop multivalent vaccines against enteric bacterial pathogens including Shigella spp. and Vibrio cholerae. His research program has been largely funded by NIH and USDA-NIFA and private funding agencies, including PATH and the National Pork Board.
NIH R01AI121067-01A1 A broadly protective subunit vaccine against enterotoxigenic Escherichia coli 9/1/16- 8/30/21. Role: PI.
USDA/NIFA 2017-67015-26632 A broadly protective vaccine against porcine post-weaning diarrhea (PWD). 5/15/2017 - 5/14/2022. Role: PI
NIH HHSN2722012000051 (NIH Pre-Clinical Service) PDP - MecVax, A multivalent subunit vaccine against enterotoxigenic E. coli (ETEC)-associated diarrhea.
NIH R21AI109209-02 A broadly protective vaccine against enterotoxigenic Escherichia coli associated travelers’ diarrhea.
EVI/PATH BMGF A broadly protective subunit vaccine against ETEC diarrhea.
EVI/PATH BMGF STa Toxoid Vaccine Consortium project: A toxoid vaccine against heat-stable enterotoxin of E. coli – Phase 3.
EVI/PATH BMGF STa Toxoid Vaccine Consortium project: A toxoid vaccine against heat-stable enterotoxin of E. coli – Phase 2.
- 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. Accepted.
- Lu, T, H. Seo, RA Rodney, W. Zhang*. 2019. Mapping the neutralizing epitopes of F18 fimbrial adhesin subunit FedF of enterotoxigenic Escherichia coli (ETEC). 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 Lett. 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). Front. Microbiol., 9:e1198.
- Nandre R., X 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).
- Duan, QD, KH Lee, RM Nandre, C Garcia, J Chen, W Zhang*. 2017. MEFA (multiepitope fusion antigen)-novel technology for structural vaccinology, proof from computational and empirical immunogenicity characterization of an enterotoxigenic Escherichia coli (ETEC) adhesin MEFA. J. Vaccines Vaccin. 8(4):1000367.
- Wenzel H, RW Kaminski, KA Clarkson, M Maciel Jr., MA Smith, W Zhang, EV Oaks. 2017. Summary of the workshop “Improving chances for successful clinical outcomes with better preclinical models”. Vaccine 35(2017):6798-6802.
- Duan, QD, W. Zhang*. 2017. Genetic fusion protein 3xSTa-ovalbumin is an effective coating antigen for ELISA to titrate anti-STa antibodies. Microbiol. Immunol. 61(7):251-257.
- Rausch, D., X. Ruan, R. Nandre, Q. Duan, E. Hashish, TA Casey, and W Zhang*. 2017. Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile (LT), heat-stable toxins (STa, STb), and Shigella toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC). Vet. Microbiol. 202(2017):79-89.
- Nandre, R.M., Q. Duan, Y. Wang, and W. Zhang*. 2016. Passive antibodies derived from intramuscularly immunized toxoid fusion 3xSTaN12S-dmLT protect against STa+ enterotoxigenic Escherichia coli (ETEC) diarrhea in a pig model. Vaccine 35:552-556.
- Nandre, R.M., X. Ruan, Q. Duan, and W. Zhang*. 2016. Enterotoxigenic Escherichia coli heat-stable toxin and heat-labile toxin toxoid fusion 3xSTaN12S-dmLT induces neutralizing anti-STa antibodies in subcutaneously immunized mice. FEMS Microbiol. Let. 363 (21):1-6.
- Nandre, R. M., X. Ruan, Q. Duan, D.A. Sack, and W. Zhang*. 2016. Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA. Vaccine 34 (2016):3620-3625.