Program Advancing Vaccines against Infectious Diseases (PAVID)

Infectious diseases continue to be a leading cause of morbidity and mortality, particularly in low- to middle-income countries.  Vaccination and antibiotic treatment are considered the two most significant advances in disease prevention and control to improve human health.  Vaccines that reduce disease severity, prevent mortality, protect against infections, and eradicate infectious pathogens are estimated to save two to three million lives each year, and become even more significant as pathogens acquire resistance to antibiotics at an alarmingly increasing rate.

Currently, the Zhang laboratory focuses on the development of cross-protective multivalent vaccines against enteric bacteria, including enterotoxigenic Escherichia coli (ETEC), Shigella spp., and Vibrio cholerae.  ETEC and Shigella are the most common bacteria that cause diarrhea in children aged less than five years in low- to middle-income countries (children’s diarrhea) and international travelers who travel to developing countries (travelers’ diarrhea) and are responsible for over 200,000 deaths and hundreds of millions of diarrheal clinical cases annually.  Cholera caused by Vibrio remains a significant threat to global health.  Additionally, ETEC bacteria are a primary cause of diarrhea in young animals (neonatal diarrhea) as well as diarrhea in weaned animals especially pigs (post-weaning diarrhea), resulting in significant economic losses to livestock producers worldwide and becoming a major threat to animal health and wellbeing.

Research projects in this laboratory have been supported by the National Institute of Health (NIH), the United States Department of Agriculture (USDA), the Program for Appropriate Technology in Health (PATH), and other federal or private funding agencies.

Research Projects

Development of MecVax, a cross-protective subunit vaccine for ETEC.
NIH R01AI177144-01 (W. Zhang, P Silvera, DA Sack), 6/2023 – 5/2028.
The major goal of this project is to optimize MecVax, a multivalent vaccine for enterotoxigenic Escherichia coli (ETEC), to manufacture master cell banks, and to develop analytic assays.
A cross-protective multivalent vaccine for Shigella and ETEC.
NIH R01AI175214-01 (DA Sack, W. Zhang), 3/2023 – 2/2028.
The major goal of this project is to develop a combination vaccine against enterotoxigenic Escherichia coli (ETEC) and Shigella.
Development and manufacture of toxoid fusion: Master Cell Banks.                                     
NIH NIAID HHSN272201800011I-0-759302000003-1 (NIH Pre-Clinical Service; Neubert, Andreas), 5/2018 – 5/2028.                                                                                
The major goal of this project is to develop pre-MCBs for the two antigens of MecVax, toxoid fusion 3xSTa_N12S-mnLT_R192G/L211A and CFA/I/II/IV MEFA.
A broadly protective vaccine against ETEC-associated post-weaning diarrhea in pigs.    
USDA-NIFA2017-67015-31471 (W. Zhang, RA Moxley), 5/2020 – 5/2025.                               
The major goal of this project is to develop a protective vaccine against ETEC-associated post-weaning diarrhea in pigs.
Determining the effect of maternal antibodies on a pig post-weaning diarrhea vaccine.                                                                                                                        
USDA-AES ILLU-7004338 (W Zhang), 10/2022 – 9/2024.                                                   
The major goal of this project is to determine the significance of passive maternal antibodies towards the active immunization of a PWD vaccine.

(Recently Completed Research Projects)

A broadly protective subunit vaccine against enterotoxigenic Escherichia coli (ETEC) associated diarrhea.                                                                                                                      
NIHR01AI121067 (W Zhang, DA Sack)  5/2016 – 4/2023                                                         
The major goal is to develop a broadly protective vaccine for ETEC by using a novel vaccinology platform and fusion protein antigens.
A multivalent oral vaccine against enterotoxigenic Escherichia coli and enteric fevers.       
NIH R43AI127050 (KL Sim, W Zhang, DA Sack)  8/2016 – 7/2019
The major goal of this project is to develop a live vaccine against ETEC diarrhea and typhoid fever.
MecVax, A multivalent subunit vaccine against enterotoxigenic E. coli (ETEC)-associated diarrhea
NIH HHSN2722012000051 (Advanced Bioscience Laboratories)   9/2015 – 10/2018                                                   
The goal is to develop a product development plan for an ETEC protein-based subunit vaccine composed of toxoid fusion 3xSTa_N12S-mnLT_R192G/L211A and CFA/I/II/IV MEFA proteins.
A toxoid vaccine against heat-stable enterotoxin of E. coli.
PATH (BMGF) consortium project (JP Natano, EM Barry, JD Clements, H Sommerfelt, W Zhang)  11/2013- 10/2018.
The goal is to identify the optimal STa toxoid (non-toxic but antigenic) for ETEC vaccine development.
A broadly protective vaccine against ETEC diarrhea.
PATH (BMGF)  (W Zhang, DA Sack)  9/2015 – 8/2018
The goal is to determine the optimal dosage of two administrated fusion proteins for vaccine development against ETEC diarrhea.