The proposal is aimed at continuing Dr. Briles' research efforts in the study of pneumococcal surface antigens. The application focuses on the first cell-associated protein described, PspA, as well as a second newly discovered protein, PspC. These two proteins may serve as vaccines themselves or as protein carriers for capsular polysaccharide-protein conjugates. PspA is present on all pneumococcal strains and can elicit protective immunity against sepsis and nasopharyngeal carriage in mice. PspC is related to PspA, but larger in size, and shows virtual identity with PspA in its C-terminal half. The proposed studies will determine whether PspC is a virulence factor and whether it can elicit protection. The relative roles of PspA and PspC in virulence and carriage in nonimmune animals will be examined. In addition, the relative roles of immunity against PspA and PspC in carriage, sepsis, and spread of pneumococci from the nasopharynx will be explored. The ability of human antibody to these molecules to protect mice from infection will be evaluated. Cross-reactive regions between the PspA and PspC proteins will be identified as well as the regions of each molecule most useful as a vaccine. Immunity to PspA and PspC will be evaluated to determine whether it involves opsonization, blocks virulence functions, or acts by other mechanisms. The data obtained will assist with the development of correlates of protective immunity for PspA and PspC that can be applied to vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021548-16
Application #
6087557
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Klein, David L
Project Start
1984-08-01
Project End
2002-10-31
Budget Start
1999-11-01
Budget End
2001-02-28
Support Year
16
Fiscal Year
2000
Total Cost
$372,671
Indirect Cost
Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Walker, Melissa M; Novak, Lea; Widener, Rebecca et al. (2016) PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia. J Immunol 196:2239-48
Hotomi, Muneki; Yuasa, Jun; Briles, David E et al. (2016) Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization. Folia Microbiol (Praha) 61:375-83
Dennis, Evida A; Coats, Mamie T; Griffin, Sarah E et al. (2015) The Effects of CFTR and Mucoid Phenotype on Susceptibility and Innate Immune Responses in a Mouse Model of Pneumococcal Lung Disease. PLoS One 10:e0140335
Kim, Ji-Yun; Paton, James C; Briles, David E et al. (2015) Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia. Oncotarget 6:44161-78
Schachern, Patricia A; Tsuprun, Vladimir; Ferrieri, Patricia et al. (2014) Pneumococcal PspA and PspC proteins: potential vaccine candidates for experimental otitis media. Int J Pediatr Otorhinolaryngol 78:1517-21
Zhao, H; Jung, J A; Briles, D E et al. (2013) Asthma and antibodies to pneumococcal virulence proteins. Infection 41:927-34
Genschmer, Kristopher R; Accavitti-Loper, Mary Ann; Briles, David E (2013) A modified surface killing assay (MSKA) as a functional in vitro assay for identifying protective antibodies against pneumococcal surface protein A (PspA). Vaccine 32:39-47
Ren, Bing; Li, Jie; Genschmer, Kristopher et al. (2012) The absence of PspA or presence of antibody to PspA facilitates the complement-dependent phagocytosis of pneumococci in vitro. Clin Vaccine Immunol 19:1574-82
Park, In Ho; Kim, Kyung-Hyo; Andrade, Ana Lucia et al. (2012) Nontypeable pneumococci can be divided into multiple cps types, including one type expressing the novel gene pspK. MBio 3:
Singh, Rajesh; Singh, Shailesh; Briles, David E et al. (2012) CCL5-independent helper T lymphocyte responses to immuno-dominant pneumococcal surface protein A epitopes. Vaccine 30:1181-90

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