The overall goal of this project is to develop a safe and effective vaccine that would prevent group A streptococcal infection. Previous studies have shown that M proteins, the major protective antigens of these organisms, contain both protective as well as potentially harmful tissue- crossreactive epitopes. The previous funding period focused on the identification of protective epitopes of """"""""rheumatogenic"""""""" M proteins and their separation from the potentially harmful autoimmune epitopes.
The Specific Aims for this renewal proposal are: 1) To determine the primary structures of defined regions of selected serotypes of M proteins that contain protective as opposed to tissue-crossreactive epitopes. 2) To construct recombinant, multivalent M protein vaccines and to determine protein conformations that evoke optimal protective immune responses in laboratory animals. 3) To determine indirectly the potential protective efficacy of multivalent M protein vaccines. 4) To develop strategies of mucosal delivery of multivalent M proteins that evoke local and systemic protective immune response. 5) To determine the minimal primary structures of selected M proteins that are capable of activating bactericidal T lymphocytes in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI010085-35
Application #
2886310
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
1996-06-01
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
35
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
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Salehi, Sanaz; Hohn, Claudia M; Penfound, Thomas A et al. (2018) Development of an Opsonophagocytic Killing Assay Using HL-60 Cells for Detection of Functional Antibodies against Streptococcus pyogenes. mSphere 3:
Wozniak, Aniela; Scioscia, Natalia; GarcĂ­a, Patricia C et al. (2018) Protective immunity induced by an intranasal multivalent vaccine comprising 10 Lactococcus lactis strains expressing highly prevalent M-protein antigens derived from Group A Streptococcus. Microbiol Immunol 62:395-404
Courtney, Harry S; Niedermeyer, Shannon E; Penfound, Thomas A et al. (2017) Trivalent M-related protein as a component of next generation group A streptococcal vaccines. Clin Exp Vaccine Res 6:45-49
Dale, James B; Smeesters, Pierre R; Courtney, Harry S et al. (2017) Structure-based design of broadly protective group a streptococcal M protein-based vaccines. Vaccine 35:19-26
Engel, Mark E; Cohen, Karen; Gounden, Ronald et al. (2017) The Cape Town Clinical Decision Rule for Streptococcal Pharyngitis in Children. Pediatr Infect Dis J 36:250-255
Fischetti, Vincent A; Dale, James B (2016) One More Disguise in the Stealth Behavior of Streptococcus pyogenes. MBio 7:
Tapia, Milagritos D; Sow, Samba O; Tamboura, Boubou et al. (2015) Streptococcal pharyngitis in schoolchildren in Bamako, Mali. Pediatr Infect Dis J 34:463-8
Dale, James B; Niedermeyer, Shannon E; Agbaosi, Tina et al. (2015) Protective immunogenicity of group A streptococcal M-related proteins. Clin Vaccine Immunol 22:344-50
Niedermeyer, Shannon E; Penfound, Thomas A; Hohn, Claudia et al. (2014) Group A streptococcus expresses a trio of surface proteins containing protective epitopes. Clin Vaccine Immunol 21:1421-5

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