Staphylococcus aureus is the most commonest cause of skin and soft tissue infections. Additionally, severe invasive S. aureus disease results in hospitalization with high mortality. An epidemic of S aureus infections has occurred in the United States in the past decade. The great majority of these infections are community associated and are methicillin-resistant, i.e. resistant to all beta-lactam antibiotics with the exception of ceftaroline. A recent annualized US study of the incidence of invasive S aureus infections estimated 600 infections occurred per 100,000 population. Therefore, there may be 1.8 million cases of S aureus infections per year in the United States alone, more than 90% of which are SSTIs. This epidemic of S aureus infections has complicated treatment and focused efforts on prevention. Prevention of Staphylococcus aureus infections by vaccination has not been simple. A number of unsuccessful vaccine trials have evaluated the protective effect of several putative protective antigens in recent years including capsular polysachharides, lipoteichoic acid, isdB and clfA. Our proposal seeks to capitalize on new ideas about how to protect against S aureus disease. Specifically, we screen antigens in collaboration with Merck Laboratories, the Brigham and Women's Hospital at Harvard University, and several derived from immunologic evaluation of convalescent sera from experimental animals to characterize protective vaccine antigen in murine models of skin infections and invasive disease with the goal to identify an optimal protective antigen combination. Following its identification, the mechanism(s) by which the new combination vaccine works will be sought. Specifically assessed will be traditional production of opsonophagocytic antibody but also the selective recruitment of lymphocyte subsets and cytokine pathways. It is expected that our combination vaccine development protocol will offer new insight into strategies for protection against invasive disease and SSTIs.

Public Health Relevance

The application seeks to assess, identify and formulate a vaccine against Staphylococcus aureus. It will accomplish this by screening 3 antigen collections for efficacy in distinct, murine models of S. aureus infection and select the optimal combination of vaccine antigens. The immunologic mechanism by which protection occurs will be evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI103342-02
Application #
8707960
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Zou, Lanling
Project Start
2013-08-01
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Chicago
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60637
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