Salmonella infections (salmonellosis) are a major public health problem throughout the world. With the emergence of multidrug resistant Salmonella strains, there is a pressing need for new methods to prevent salmonellosis. As there are characteristic carbohydrate structures on the surface of Salmonella bacteria, in this project, a collaborative team is formed to develop effective carbohydrate based anti-Salmonella vaccines. Instead of relying on isolated carbohydrates from the pathogenic bacteria, in aim 1, synthetic strategies will be developed to produce structure well defined Salmonella glycans from major pathogenic serovars.
In aim 2, Salmonella glycans will be conjugated with a virus like particle, bacteriophage Q? as potential vaccines targeting specific pathogenic Salmonella strains. This is supported by promising preliminary results that the Q? glycan conjugates were able to induce high titers (over 80 million ELISA units in rabbits) and long lasting anti-glycan IgG antibodies, which could provide complete protection to mice from lethal challenges by Salmonella bacteria. Building on these results, the Q? carrier will be engineered to enhance its abilities to further boost anti-Salmonella immune responses.
In aim 3, a broad spectrum anti- Salmonella vaccine will be developed, which can provide powerful protection against multiple types of major pathogenic Salmonella by a single vaccine. This can complement well the strain specific vaccines. This work can lead to an exciting new direction for anti-Salmonella vaccine development, providing a much needed new arsenal in fighting salmonellosis.

Public Health Relevance

Salmonella infections are a serious public health problem throughout the world. In this project, carbohydrate based anti-Salmonella vaccines will be developed to protect the immunized host from the infections of multiple types of Salmonella, and to reduce the emergence of multidrug resistant Salmonella strains.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI146210-01
Application #
9798692
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Alexander, William A
Project Start
2019-07-16
Project End
2024-06-30
Budget Start
2019-07-16
Budget End
2020-06-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Michigan State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824