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Faculty Detail    
Name DAVID E BRILES
  
Campus Address BBRB 276 Zip 2170
Phone  (205) 934-9339
E-mail  dbriles@uab.edu
Other websites PubMed Listing
Curriculum Vitae
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Professor Emeritus

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Immunology 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 
Microbiology 

Biographical Sketch 
David E. Briles (b.1945), Professor of Microbiology, Genetics and Pediatrics, did his graduate work on the genetic regulation of antibody binding site structure at The Rockefeller University in New York City with Dr. Richard Krause. Dr. Briles' postdoctoral studies, with Dr. Joseph Davie at Washington University Medical School in St. Louis, dealt with the expression of antibody diversity in antibacterial antibody responses and the genetic control of susceptibility of mice to Salmonella and pneumococcal infection. He joined the UAB faculty in 1978. His research is on the molecular biology and genetics of bacterial pathogenesis, bacterial vaccines, and epidemiology of bacterial infections. Together with other colleagues at UAB and past trainees he was awarded a number of patents on pneumococcal vaccine antigens. His present studies are on protein virulence factors of pneumococci, their mechanisms of action and potential use in vaccines. In recent years his lab worked to develop surrogate assays for protective immunity to pneumococcal protein antigens. Dr. Briles has served on several study sections at the NIH and FDA and several editorial boards. He has been an advisor about the potential of pneumococcal proteins as human vaccine to the WHO, PAHO, FDA, and the PATH foundation. Dr. Briles has been a visiting faculty member at SungKyunKwan University in South Korea where he spent two months for 5 year as a WCU scholar. He is also an Adjunct Professor at Northern Illinois University, DeKalb, Illinois. Dr. Briles is married and has two grown children. His hobby is tree farming.

Society Memberships
Organization Name Position Held Org Link
American Academy of Microbiology ~1998 – present   Fellow   
American Association for the Advancement of Science  Fellow   
American Association for the Advancement of Science (AAAS)  Member   
American Association of Immunologists  Member   
American Society for Microbiology (ASM)   Member   
Infectious Disease Society of America  Member   
National Academy of Inventors  Fellow   
 



Research/Clinical Interest
Title
Pneumococcal virulence factors; mechanisms of action and use in vaccine
Description
We study the interactions of host defenses and bacterial virulence factors in the pathogenesis of bacteria. Our approach is to use both bacterial and animal genetics to identify and study important mechanisms in protection and virulence. We have identified a cell wall protein of pneumococci, PspA, which is important for pneumococcal virulence and which could be useful as a vaccine for very young children. Studies are underway to characterize the protection-eliciting portions of PspAs from different childhood strains of pneumococci, and to assemble these into an effective human vaccine with other pneumococcal proteins. We are studying the mode of action of several pneumococcal virulence factors including PspA, pneumolysin, PspC, PsaA, PcpA, and NanA, and are investigating the possibility of developing a pneumococcal vaccine that would prevent pneumococcal carriage. In other studies, we are investigating the effects of specific immunity and inflammation induced host immunity on the in vivo killing and growth rates of Streptococcus pneumoniae. In collaboration with Drs. Crain in Pediatrics and Nahm in Pathology, we have examined the changing distributions of capsular polysaccharides and protein antigens in human pneumococcal isolates.

Selected Publications 
Publication PUBMEDID
Briles DE, SK Hollingshead, J King, A Swift. PA Braun, MK Park, LM Ferguson, MH Nahm, GS Nabors. Immunization of humans with rPspA elicits antibodies, which passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA. J. Infect. Dis. 182: 1694-1701. 2000.   11069242 
DE Briles, SK. Hollingshead, JC. Paton, EW. Ades, L Novak, FW. van Ginkel, and WH, Benjamin Jr. Immunization with PspA and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae. J. Infect. Dis. 188: 339-348. 2003  12870114 
Ren B, MA McCory, C Pass, DC Bullard, CM Ballantyne, Yuanyuan Xu, DE Briles, AJ Szalai. The virulence function of Streptococcus pneumoniae surface protein A (PspA) involves inhibition of complement activation and impairment of complement receptor-mediated protection. J. Immunol. 173: 7506-7512. 2004.   15585877 
Benjamin WH Jr, P Hall, DE Briles: A hemA mutation renders S. typhimurium avirulent in mice, yet capable of eliciting protection against subsequent S. typhimurium infection. Microbial Pathogenesis. 11: 289-295, 1991  1813780 
Benjamin WH Jr, J Yother, P Hall, DE Briles. The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in virulence; mutant (nonfunctional) mviA results in virulence. J. Exp. Med. 174:1073-1083, 1991.  1940789 
Daniels CC, Coan P, King J, Hale J, Benton K, DE Briles, Hollingshead SK. The proline-rich region of pneumococcal surface proteins A and C contains surface accessible epitopes common to all pneumococci and elicits antibody-mediated protection against sepsis. Infect. Immun. PMCID 2863538. 78:2163-72. 2010.  20194601 
Mirza S, L Wilson, WH Benjamin Jr, J Novak, S. Barns, SK Hollingshead, DE Briles. Serine protease PrtA from Streptococcus pneumoniae plays a role in the killing of S. pneumoniae by apolactoferrin. Infect Immun 79:2440-24450. PMCID 3125832. 2011.  21422179 
Benjamin, WH Jr, P Hall, SJ Roberts, DE Briles: The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing. J. Immunol. 144:3143-3151, 1990.  2182715  
Mukerji R, S Mirza, AM Roche, RW Widener, CM Croney, DK Rhee, JN Weiser, AJ Szalai, DE Briles. Pneumococcal surface protein A inhibits complement deposition on the pneumococcal surface by competing with the binding of C-reactive protein to cell-surface phosphocholine. J Immunol 189:5327-5335. PMCID 3517878 2012.   23105137 
Daniels CC, K-H Kim, RL. Burton, S Mirza, M Walker, J King, Y Hale, P Coan, D-K Rhee, MH Nahm, and DE Briles. Modified opsonization, phagocytosis, and killing assays to measure potentially protective antibodies against pneumococcal surface protein A. Clin Vaccine Immunol 20:1549-1558. PMCID 3807198. 2013.  23925886 
Genschmer, KR, MA Accavitti-Loper, DE Briles. A modified surface killing assay (MSKA) as a functional in vitro assay for identifying protective antibodies against pneumococcal surface protein A (PspA). Vaccine 32:39-42.PMCID 3893085 2014  24211169 
Kothari, N, S Kothari, YJ Choi, A Dey, DE. Briles, DK Rhee, and R Carbis. A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi. Vaccine 33:783-788. PMID 25545593 2015.  25545593  
Fukuyama Y, Y Yuki, Y Katakai, N Harada, H Takahashi, S Takeda, M Mejima, S Joo, S Kurokawa, S Sawada, H Shibata, EJ Park, K Fujihashi, DE Briles, Y Yasutomi, H Tsukada, K Akiyoshi, H Kiyono. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques, January 2015 Mucosal Immunology. 8:1144-1153. PMCID4762909. 2015  25669148  
Hotomi M, J Yuasa, DE Briles, N Yamanaka. Pneumolysin plays a key role in the initial step of establishing nasal colonization. Folia Microbiol (Praha) 61:355-383. PMID: 26803756 2016.  26803756 
Walker, MM, L Novak, R Weidner, JA Grubbs, J King, JY Hale, MM Ochs, LE Myers, DE Briles, J Deshane. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia. J Immunol. 196:2239-48. PMCID 4761482. 2016  26829988 
Hatcher BL, JY Hale, DE Briles. Free Sialic Acid: A Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System. Infect. Immun. 84:2607- 2615. PMCID 4995916. 2016.   27354445 
Mirza S., Benjamin, WH Coan, Hwang S-A, Winslett A-K, Yother J, Hollingshead SK, Fujihashi K, Briles DE. The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin. Microbial Pathogenesis. 99: 209-219. PMID27569531 2016.   27569531 
Mirza S., Benjamin, WH Coan, Hwang S-A, Winslett A-K, Yother J, Hollingshead SK, Fujihashi K, Briles DE. The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin. Microbial Pathogenesis. 99: 209-219. PMID27569531 2016.  27569531  
Benjamin WH Jr, CL Turnbough Jr, BS Posey, DE Briles: The ability of Salmonella typhimurium to produce the siderophore enterobactin is not a virulence factor in mouse typhoid. Infect. Immun. 50:392-397, 1985  2932389  
Briles DE, JL Claflin, K Schroer, C Forman: Mouse IgG3 antibodies are highly protective against infection with Streptococcus pneumoniae. Nature. 294:88-90, 1981  6170000  
McDaniel LS, G Scott, JF Kearney, DE Briles: Monoclonal antibodies against protease sensitive pneumococcal antigens can protect mice from fatal infection with Streptococcal pneumoniae. J. Exp. Med. 160:386-397, 1984.  6381634  
McDaniel LS, WH Benjamin Jr, C Forman, DE Briles: Blood clearance by anti-phosphocholine antibodies as a mechanism of protection in experimental pneumococcal bacteremia. J. Immunol. 133:3308-3312, 1984  6491288 
Briles DE, C Forman, S Hudak, JL Claflin: Anti-PC antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J. Exp. Med. 156:1177-1185, 1982   7153709 
Briles DE, M Nahm, K Schroer, J Davie, P Baker, JF Kearney, R Barletta: Anti-phosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 S. pneumoniae. J. Exp. Med. 153:694-705, 1981.  7252411 
McDaniel LS, BA Ralph, DO McDaniel, DE Briles. Localization of protection eliciting epitopes on PspA (Pneumococcal Surface Protein A) of Streptococcus pneumoniae between amino acid residues 192 and 260. Microbial Pathogenesis. 17:323-337. 1994   7723659  
Wu H-Y, MH Nahm, Y Guo, MW. Russell, DE Briles. Intranasal immunization of mice with PspA (Pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae. J. Infect. Dis. 175:839-846. 1997  9086139 
 

Keywords
Streptococcus pneumoniae, virulence, host immunity, vaccines, virulence factors, mechanisms of virulence, vaccine antigens