To date, no vaccine to prevent Staphylococcus aureus infection has succeeded in Phase III clinical trials. Meanwhile, the need for a vaccine continues to escalate as does the ability of this pathogen to acquire antibiotic resistance. Our goal is to demonstrate the effectiveness of virus-like particles (VLPs) as an innovative broad- spectrum platform for production of vaccines against S. aureus secreted virulence factors. VLPs are a novel approach to the design of vaccines targeting bacterial infection and the ability of VLP-based vaccines targeting secreted S. aureus toxins to induce a protective immune response has not been investigated. Therefore, the goal of this proposal is to test the hypothesis that presentation of toxin peptides on VLPs can be used to induce adaptive immunity targeting major S. aureus secreted virulence factors. To test this hypothesis we will pursue the following specific aims:
Specific Aim #1 : To determine the immunogenicity and efficacy of VLPs displaying structurally selected Hla and bi-component leukotoxin peptides in nave and S. aureus colonized mice.
Specific Aim #2 : To determine the immunogenicity and efficacy of VLPs displaying 10-mer peptides representing the toxin peptidome of Hla and bi-component leukotoxins in nave and S. aureus colonized mice. Importantly, unlike other platforms and experimental adjuvants, VLPs are currently used in FDA-approved vaccines (like the current HPV vaccines). Therefore, if experimental approaches using VLPs are confirmed in animal models, they can potentially translate into human trials fairly readily.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI114706-01A1
Application #
8967305
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Zou, Lanling
Project Start
2015-07-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of New Mexico Health Sciences Center
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Daly, Seth M; Joyner, Jason A; Triplett, Kathleen D et al. (2017) VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation. Sci Rep 7:637
Krute, Christina N; Krausz, Kelsey L; Markiewicz, Mary A et al. (2016) Generation of a Stable Plasmid for In Vitro and In Vivo Studies of Staphylococcus Species. Appl Environ Microbiol 82:6859-6869