Research Topics
| David BrilesSummaryAffiliation: University of Alabama at Birmingham Country: USA Publications
Research Grants
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Publications
Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniaeD E Briles
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 68:796-800. 2000..As PspA and pneumolysin are known to elicit immunity to bacteremia and pneumonia, their inclusion in a mucosal vaccine may enable such a vaccine to prevent invasive disease as well as carriage...
The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infectionD E Briles
Department of Microbiology, University of Alabama at Birmingham, 658 BBLB, 845 19th Street South, Birmingham, AL 35294, USA
Vaccine 18:1707-11. 2000..The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6...
Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspAD E Briles
Departments of Microbiology and Pediatrics, University of Alabama at Birmingham, AL 35294, USA
J Infect Dis 182:1694-701. 2000..pneumoniae expressing either family 1 or 2 PspAs and with strains of all 3 capsular types tested: 3, 6A, and 6B. These studies suggest that PspA may have efficacy as a human vaccine...
The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniaeD E Briles
Department of Microbiology, University of Alabama at Birmingham UAB, Birmingham, AL 35294 2170, USA
Vaccine 19:S87-95. 2000..The inclusion of a few of these proteins into the polysaccharide-protein conjugate vaccines may be able to enhance their efficacy against otitis media and might be able to constitute a successful all-protein pneumococcal vaccine...
Protection of the elderly from pneumococcal pneumonia with a protein-based vaccine?David E Briles
Department of Microbiology, University of Alabama at Birmingham, Suite 258 11, Bevill Biomedical Research Building, 1530 3rd Avenue South, Birmingham, AL 35294 2170, USA
Mech Ageing Dev 125:129-31. 2004..PspA has been used in human safety trials and was shown to elicit antibodies that can protect mice from otherwise fatal pneumococcal infections...
Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniaeDavid E Briles
Department of Microbiology, University of Alabama at Birmingham, USA
J Infect Dis 188:339-48. 2003....
Elicitation of mucosal immunity by proteins of Streptococcus pneumoniaeDavid E Briles
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 2170, USA
Adv Otorhinolaryngol 72:25-7. 2011..3) Complement-fixing IgG antibody can protect against colonization and may act by protecting against colonization of bacteria...
Nasal colonization with Streptococcus pneumoniae includes subpopulations of surface and invasive pneumococciDavid E Briles
Department of Microbiology, University of Alabama at Birmingham, USA
Infect Immun 73:6945-51. 2005..Although this speculation is unproven, the observation that there are separate populations of pneumococci during colonization may help guide future attempts to understand the biology of nasal colonization by this pathogen...
Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniaePriya Balachandran
Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 70:2526-34. 2002..This latter finding strongly indicates that pneumococci are actively metabolizing and growing while in the nasopharynx...
Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection modelHazeline Roche
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 71:1033-41. 2003..These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection...
Relative roles of genetic background and variation in PspA in the ability of antibodies to PspA to protect against capsular type 3 and 4 strains of Streptococcus pneumoniaeHazeline Roche
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 71:4498-505. 2003..These results point out the importance of including more than one PspA in any PspA vaccines developed for human use...
The virulence function of Streptococcus pneumoniae surface protein A involves inhibition of complement activation and impairment of complement receptor-mediated protectionBing Ren
Department of Microbiology, University of Alabama, Birmingham, AL 35294, USA
J Immunol 173:7506-12. 2004..Our new results suggest that complement receptors CR1/2, CR3, and CR4 all play important roles in host defense against pneumococcal infection...
Mn2+-dependent regulation of multiple genes in Streptococcus pneumoniae through PsaR and the resultant impact on virulenceJason W Johnston
Department of Microbiology, University of Iowa, BSB 3 401, 51 Newton Road, Iowa City, IA 52242, USA
Infect Immun 74:1171-80. 2006..Neither PcpA nor PsaR was found to be required for colonization of the nasopharynx in a carriage model. This is the first demonstration of Mn2+ acting as a signal for the expression of virulence factors within different host sites...
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 sepsisCalvin C Daniels
Department of Microbiology, University of Alabama at Birmingham, 1530 3rd Ave South, Birmingham, AL 35294 2170, USA
Infect Immun 78:2163-72. 2010..Due to their conservation and cross-reactivity, the PR regions and NPB regions represent potential vaccine targets capable of eliciting cross-protection immunity against pneumococcal infection...
Immunogenic protein contaminants in pneumococcal vaccinesJigui Yu
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
J Infect Dis 187:1019-23. 2003..The degree of contamination was highly variable, and this should be considered in pneumococcal vaccine evaluations or when capsular polysaccharide is used for pneumococcal antibody assays...
Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsisDavid T Glover
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
Infect Immun 76:2767-76. 2008..In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci...
PspA and PspC minimize immune adherence and transfer of pneumococci from erythrocytes to macrophages through their effects on complement activationJie Li
Department of Microbiology, University of Alabama at Birmingham, AL 35294, USA
Infect Immun 75:5877-85. 2007..These data provide new insight into how PspA and PspC act in synergy to protect pneumococci from complement-dependent clearance during invasive infection...
Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanismOlga Senkovich
Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, AL 35294, USA
J Mol Biol 370:701-13. 2007..Insights from the structure of the complex have implications for designing therapeutic strategies for treatment and prevention of pneumococcal diseases that remain a major public health problem worldwide...
Lipoprotein PsaA in virulence of Streptococcus pneumoniae: surface accessibility and role in protection from superoxideJason W Johnston
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 72:5858-67. 2004..This implies that superoxides are a key player in oxidative stress generated in the presence of iron...
Capsule does not block antibody binding to PspA, a surface virulence protein of Streptococcus pneumoniaeCalvin C Daniels
Department of Microbiology, University of Alabama at Birmingham, BBRB, 1530 3rd Ave North, Birmingham, AL 35294, USA
Microb Pathog 40:228-33. 2006..The binding of antibody to PC was largely, but not completely, blocked by capsular polysaccharide...
Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surfaceBing Ren
Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 72:114-22. 2004..Antibodies to PspA could overcome the anticomplementary effect of PspA, allowing for increased complement activation and C3 deposition onto PspA+ bacteria...
Pneumococcal carriage results in ganglioside-mediated olfactory tissue infectionFrederik W van Ginkel
Department of Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294 2170, USA
Proc Natl Acad Sci U S A 100:14363-7. 2003..These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport...
Evolution and virulence of serogroup 6 pneumococci on a global scaleD Ashley Robinson
Department of Microbiology, University of Alabama at Birmingham, 35294, USA
J Bacteriol 184:6367-75. 2002..001), and the ancestors tended to be less virulent than their descendents in a mouse model of infection. These data suggested that virulent serogroup 6 clones have evolved multiple times from less-virulent ancestral clones...
Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniaeBing Ren
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 71:75-85. 2003..These results suggest that family 1 and family 2 PspA proteins play similar roles in virulence and that surface accessibility of PspA is important for their function...
Secretory-IgA antibodies play an important role in the immunity to Streptococcus pneumoniaeYoshiko Fukuyama
Department of Pediatric Dentistry, Immunobiology Vaccine Center, Institute of Oral Health Research, University of Alabama at Birmingham, SDB 801A1, 1919 7th Avenue South, Birmingham, AL 35294 0007, USA
J Immunol 185:1755-62. 2010..These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity...
Pneumococcal surface protein A (PspA) family distribution among clinical isolates from adults over 50 years of age collected in seven countriesSusan K Hollingshead
Department of Microbiology, University of Alabama at Birmingham, BBRB 658, AL 35294, USA
J Med Microbiol 55:215-21. 2006..In conclusion, inclusion of PspA family 1 and family 2 in future pneumococcal vaccines would ensure broad coverage of pneumococcal strains infecting people over 50 years of age...
PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin [corrected]Mirza Shaper
Department of Microbiology, University of Alabama at Birmingham, USA
Infect Immun 72:5031-40. 2004..Antibody to PspA enhanced killing by lactoferrin. These findings suggested that the binding of ALF to PspA probably blocks the active site(s) of ALF that is responsible for killing...
Complement receptor 1 expression on mouse erythrocytes mediates clearance of Streptococcus pneumoniae by immune adherenceJie Li
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Infect Immun 78:3129-35. 2010..These data support that immune adherence via CR1 on erythrocytes likely plays an important role in the clearance of opsonized bacteria from human blood...
Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniaeCrystal N Johnson
University of Alabama at Birmingham, Birmingham, Alabama 35249, USA
Emerg Infect Dis 11:814-20. 2005..However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030...
Antibody to the type 3 capsule facilitates immune adherence of pneumococci to erythrocytes and augments their transfer to macrophagesJie Li
Department of Microbiology, University of Alabama at Birmingham, 1530 3rd Ave South, Birmingham, AL 35294 2170, USA
Infect Immun 77:464-71. 2009....
Characterization of the dihydrolipoamide dehydrogenase from Streptococcus pneumoniae and its role in pneumococcal infectionAlexander W Smith
Department of Microbiology, University of Alabama at Birmingham, BBRB 673 Box 10, 658 Bevill Building, 854 19th Street South, 35294, USA
Mol Microbiol 44:431-48. 2002..The DLDH-negative bacteria produced only 50% of normal capsular polysaccharide, a phenotype that may be associated with impaired carbohydrate metabolism...
PIR-B-deficient mice are susceptible to Salmonella infectionIkuko Torii
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 3300, USA
J Immunol 181:4229-39. 2008..These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection...
Serine protease PrtA from Streptococcus pneumoniae plays a role in the killing of S. pneumoniae by apolactoferrinShaper Mirza
Department of Microbiology, Division of Epidemiology, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294 2170, USA
Infect Immun 79:2440-50. 2011....
Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniaeAbiodun D Ogunniyi
School of Molecular and Biomedical Science, The University of Adelaide, SA 5005, Australia
Infect Immun 75:350-7. 2007..To date, the combination of PdB, PspA, and PspC offers the best protection...
Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriageRavichandran Palaniappan
Department of Pharmaceutical Sciences, Southern School of Pharmacy, Atlanta, GA 30310-1495, USA
Infect Immun 73:1006-13. 2005..Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage...
Distribution of pneumococcal surface protein A families 1 and 2 among Streptococcus pneumoniae isolates from children in finland who had acute otitis media or were nasopharyngeal carriersMerit M Melin
National Public Health Institute KTL, Department of Vaccines, Mannerheimintie 166, 00300 Helsinki, Finland
Clin Vaccine Immunol 15:1555-63. 2008..The majority of the isolates (97%) belonged to either PspA family 1 or family 2, suggesting that a combination including the two main PspA families would make a good vaccine candidate...
Development of antibodies to PspA families 1 and 2 in children after exposure to Streptococcus pneumoniaeMerit M Melin
National Public Health Institute KTL, Department of Vaccines, Mannerheimintie 166, 00300 Helsinki, Finland
Clin Vaccine Immunol 15:1529-35. 2008..The results suggest that children have a relatively family-specific antibody response to the PspA family they have been exposed to and that any PspA vaccine for children should contain members of both major PspA families...
Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal diseaseLaurence Baril
Aventis Pasteur, Lyon, France
Vaccine 23:789-93. 2004..In contrast, acute and convalescent antibody levels were similar in control patients with invasive diseases due to other microorganisms...
Increased protection against pneumococcal disease by mucosal administration of conjugate vaccine plus interleukin-12Joyce M Lynch
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208, USA
Infect Immun 71:4780-8. 2003..We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage...
Effects of zinc deficiency and pneumococcal surface protein a immunization on zinc status and the risk of severe infection in miceTor A Strand
Centre for International Health and Department of Microbiology and Immunology, The Gade Institute, University of Bergen, Bergen N 5021, Norway
Infect Immun 71:2009-13. 2003..PspA immunization reduced the risk of severe disease, and the reduction in severity was reflected in substantially reduced zinc depletion from bones...
Antibodies to pneumococcal surface protein A families 1 and 2 in serum and saliva of children and the risk of pneumococcal acute otitis mediaBirgit Simell
Department of Vaccines, National Public Health Institute, Mannerheimintie 166, Helsinki, Finland
J Infect Dis 196:1528-36. 2007..We assessed the development of human serum and salivary antibodies against the PspA families 1 (PspA1) and 2 (PspA2) in early childhood and their role in the prevention of pneumococcal acute otitis media (AOM)...
Relationship between surface accessibility for PpmA, PsaA, and PspA and antibody-mediated immunity to systemic infection by Streptococcus pneumoniaeDennis O Gor
Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA
Infect Immun 73:1304-12. 2005..These experiments support the hypothesis that the extent of protection against systemic pneumococcal infection is influenced by target antigen accessibility to circulating host antibodies...
Contributions of pneumolysin, pneumococcal surface protein A (PspA), and PspC to pathogenicity of Streptococcus pneumoniae D39 in a mouse modelAbiodun D Ogunniyi
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia
Infect Immun 75:1843-51. 2007..These findings further demonstrate that the mechanism of pneumococcal pathogenesis is highly complex and multifactorial but ascribes a role for each of these virulence proteins, alone or in combination, in the process...
Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host defense to Streptococcus pneumoniae infection in mice: role of the CCL2-CCR2 axisChristine Winter
Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover School of Medicine, Hannover 30625, Germany
J Immunol 178:5828-38. 2007....
CCL5 modulates pneumococcal immunity and carriageRavichandran Palaniappan
Mercer University, Atlanta, GA 30341, USA
J Immunol 176:2346-56. 2006..These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity...
Vaccine-induced human antibodies to PspA augment complement C3 deposition on Streptococcus pneumoniaeMartina M Ochs
Sanofi Pasteur, Toronto, Ontario, Canada
Microb Pathog 44:204-14. 2008..A vaccine candidate that can elicit immunity that neutralizes or compensates for S. pneumoniae's ability to thwart host immunity would be of value...
Antibody-independent, CD4+ T-cell-dependent protection against pneumococcal colonization elicited by intranasal immunization with purified pneumococcal proteinsAlan Basset
Division of Infectious Diseases, Children s Hospital Boston, Enders 861 3, 300 Longwood Avenue, Boston, MA 02115, USA
Infect Immun 75:5460-4. 2007..Overall, our results show that intranasal immunization with a mixture of pneumococcal proteins protects against colonization in an antibody-independent, CD4+ T-cell-dependent manner...
FMS-like tyrosine kinase 3 ligand aggravates the lung inflammatory response to Streptococcus pneumoniae infection in mice: role of dendritic cellsChristine Winter
Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover School of Medicine, Hannover 30625, Germany
J Immunol 179:3099-108. 2007..pneumoniae, and support the concept that CCR2-dependent mononuclear phagocyte as opposed to neutrophil recruitment contributes to increased lung leakage in Flt3L-pretreated mice challenged with S. pneumoniae...
Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infectionsJae Hyang Lim
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Immunity 27:349-60. 2007..Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia...
Effect of high dose oral zinc in mice with severe infection with Streptococcus pneumoniaeBerit S H Hembre
Department of Medicine, Lovisenberg Diakonale Sykehus, Oslo, Norway
Scand J Infect Dis 40:363-7. 2008..There were no differences in the numbers of S. pneumoniae colony forming units (CFUs) in blood or nasal wash between the groups. Thus, high doses of zinc did not alter the severity of systemic pneumococcal infection in mice...
Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responsesKaren M Haas
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
Immunity 17:713-23. 2002..Thus, CD21/35 expression is critical for early protective antibody responses to lethal pathogens that rapidly multiply and quickly overwhelm the immune system...
Basophils enhance immunological memory responsesAndrea Denzel
Department of Internal Medicine II, University Hospital Regensburg, 93042 Regensburg, Germany
Nat Immunol 9:733-42. 2008..These basophil-dependent effects on B cells required interleukins 6 and 4 and increased the capacity of CD4(+) T cells to provide B cell help. Thus, basophils are important contributors to humoral memory immune responses...
Macrophage Turnover Kinetics in the Lungs of Mice Infected with Streptococcus pneumoniaeKatharina Taut
Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover School of Medicine, Hannover, Germany
Am J Respir Cell Mol Biol 38:105-13. 2008....
Research Grants
- IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEIN A AND CDavid Briles; Fiscal Year: 2002..The data obtained will assist with the development of correlates of protective immunity for PspA and PspC that can be applied to vaccine development. ..
- Mechanism of Action of Antibody to PspADavid Briles; Fiscal Year: 2003..Our analyses of the protection-eliciting and non-protection-eliciting epitopes on PspA should make it possible to design even better PspA vaccines in the future. ..
- Mechanism of Action of Antibody to PspADavid Briles; Fiscal Year: 2006..Our analyses of the protection-eliciting and non-protection-eliciting epitopes on PspA should make it possible to design even better PspA vaccines in the future. ..
- Mechanism of Action of Antibody to PspADavid Briles; Fiscal Year: 2007..Our analyses of the protection-eliciting and non-protection-eliciting epitopes on PspA should make it possible to design even better PspA vaccines in the future. ..
- MOLECULAR AND CELLULAR BACTERIAL PATHOGENESISDavid Briles; Fiscal Year: 2007..The MCBP advisory committee will advise the trainees in their research and training programs and in their search for a job or postdoctoral position at the completion of their MCBP training. ..
- PspA: A Potential Pneumococcal Vaccine ComponentDavid Briles; Fiscal Year: 2009..pneumoniae is important because of the high complexity and cost of the polysaccharide-protein conjugate vaccine and the rapid evolution of pneumococci to evade the capsule-type-specific protection elicited by the conjugate vaccine. ..
- PspA: A Potential Pneumococcal Vaccine ComponentDavid E Briles; Fiscal Year: 2010..pneumoniae is important because of the high complexity and cost of the polysaccharide-protein conjugate vaccine and the rapid evolution of pneumococci to evade the capsule-type-specific protection elicited by the conjugate vaccine. ..
- PROTECTIVE IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEIN ADavid Briles; Fiscal Year: 1993....
- PROTECTIVE IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEINSDavid Briles; Fiscal Year: 1991....
- PspA: A Potential Pneumococcal Vaccine ComponentDavid Briles; Fiscal Year: 2009..pneumoniae is important because of the high complexity and cost of the polysaccharide-protein conjugate vaccine and the rapid evolution of pneumococci to evade the capsule-type-specific protection elicited by the conjugate vaccine. ..
