Leonard A Smith

Summary

Affiliation: Walter Reed Army Medical Center
Country: USA

Publications

  1. ncbi request reprint Expression, purification, and characterization of Clostridium botulinum type B light chain
    Janice Gilsdorf
    Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702 5011, USA
    Protein Expr Purif 46:256-67. 2006
  2. ncbi request reprint Botulinum neurotoxin vaccines: past, present, and future
    Leonard A Smith
    Integrated Toxicology Division, US Army Medical Research Institute of Infectious Diseases Fort Detrick, MD 21702 5011, USA
    Crit Rev Immunol 27:303-18. 2007
  3. pmc An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock
    Garry L Morefield
    Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
    J Immune Based Ther Vaccines 6:5. 2008
  4. pmc Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies
    Suzanne R Kalb
    Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N, E, Atlanta, GA 30341, USA
    BMC Biochem 12:58. 2011
  5. doi request reprint Botulism and vaccines for its prevention
    Leonard A Smith
    Medical Countermeasures Technology, U S Army Medical Research and Materiel Command, Fort Detrick, MD 21702 5011, United States of America
    Vaccine 27:D33-9. 2009
  6. ncbi request reprint Roads from vaccines to therapies
    Leonard A Smith
    Division of Toxinology and Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702 5011, USA
    Mov Disord 19:S48-52. 2004
  7. pmc Identification and biochemical characterization of small-molecule inhibitors of Clostridium botulinum neurotoxin serotype A
    Virginia Roxas-Duncan
    Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD 21702, USA
    Antimicrob Agents Chemother 53:3478-86. 2009
  8. doi request reprint Rapid product analysis and increased sensitivity for quantitative determinations of botulinum neurotoxin proteolytic activity
    Benjamin Rowe
    Department of Cell Biology and Biochemistry, Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
    Anal Biochem 396:188-93. 2010
  9. pmc Light chain separated from the rest of the type a botulinum neurotoxin molecule is the most catalytically active form
    Nizamettin Gul
    Integrated Toxicology Division, Department of Cell Biology and Biochemistry, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
    PLoS ONE 5:e12872. 2010
  10. ncbi request reprint Protection with recombinant Clostridium botulinum C1 and D binding domain subunit (Hc) vaccines against C and D neurotoxins
    Robert P Webb
    Integrated Toxicology Division, United States Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, United States
    Vaccine 25:4273-82. 2007

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Expression, purification, and characterization of Clostridium botulinum type B light chain
    Janice Gilsdorf
    Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702 5011, USA
    Protein Expr Purif 46:256-67. 2006
    ..The synthetic BoNT/B LC has been found to be highly active on its substrate (vesicle associated membrane protein-2) and, therefore, can serve as a useful reagent for BoNT/B research...
  2. ncbi request reprint Botulinum neurotoxin vaccines: past, present, and future
    Leonard A Smith
    Integrated Toxicology Division, US Army Medical Research Institute of Infectious Diseases Fort Detrick, MD 21702 5011, USA
    Crit Rev Immunol 27:303-18. 2007
    ..Results from that study demonstrated that the recombinant bivalent vaccine was safe and well tolerated at all dosage levels tested and stimulated serotype-specific neutralizing antibodies among the majority of vaccine recipients...
  3. pmc An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock
    Garry L Morefield
    Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
    J Immune Based Ther Vaccines 6:5. 2008
    ..Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy...
  4. pmc Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies
    Suzanne R Kalb
    Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N, E, Atlanta, GA 30341, USA
    BMC Biochem 12:58. 2011
    ..However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical...
  5. doi request reprint Botulism and vaccines for its prevention
    Leonard A Smith
    Medical Countermeasures Technology, U S Army Medical Research and Materiel Command, Fort Detrick, MD 21702 5011, United States of America
    Vaccine 27:D33-9. 2009
    ..This review focuses on botulism and the development of vaccines for its prevention...
  6. ncbi request reprint Roads from vaccines to therapies
    Leonard A Smith
    Division of Toxinology and Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702 5011, USA
    Mov Disord 19:S48-52. 2004
    ..Other resources developed as part of the vaccine initiative, likewise, are finding utility in the quest to develop therapies for botulism...
  7. pmc Identification and biochemical characterization of small-molecule inhibitors of Clostridium botulinum neurotoxin serotype A
    Virginia Roxas-Duncan
    Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD 21702, USA
    Antimicrob Agents Chemother 53:3478-86. 2009
    ..This study demonstrates the utility of a multidisciplinary approach (in silico screening coupled with biochemical testing) for identifying promising small-molecule BoNT/A inhibitors...
  8. doi request reprint Rapid product analysis and increased sensitivity for quantitative determinations of botulinum neurotoxin proteolytic activity
    Benjamin Rowe
    Department of Cell Biology and Biochemistry, Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
    Anal Biochem 396:188-93. 2010
    ..Sensitivity of the assay and accuracy and rapidity of product analysis should greatly augment efforts in therapeutic development...
  9. pmc Light chain separated from the rest of the type a botulinum neurotoxin molecule is the most catalytically active form
    Nizamettin Gul
    Integrated Toxicology Division, Department of Cell Biology and Biochemistry, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
    PLoS ONE 5:e12872. 2010
    ..Our results clearly demonstrated that in vitro, the LC minus the rest of the molecule is the most catalytically active form. The results may have implication as to the identity of the active, toxic moiety of BoNT/A in vivo...
  10. ncbi request reprint Protection with recombinant Clostridium botulinum C1 and D binding domain subunit (Hc) vaccines against C and D neurotoxins
    Robert P Webb
    Integrated Toxicology Division, United States Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, United States
    Vaccine 25:4273-82. 2007
    ....
  11. doi request reprint Progress in biological threat agent vaccine development: a repeat-dose toxicity study of a recombinant ricin toxin A-chain (rRTA) 1-33/44-198 vaccine (RVEc) in male and female New Zealand white rabbits
    Daniel E McLain
    Walker Downey and Associates, Inc, Verona, WI, USA
    Int J Toxicol 30:143-52. 2011
    ..The highest immune response was observed on study day 99 (ie, 2 weeks after the last dose). The immune response observed demonstrated that RVEc is biologically active in the rabbit model, with no apparent marked sex differences...
  12. doi request reprint Identification of residues surrounding the active site of type A botulinum neurotoxin important for substrate recognition and catalytic activity
    S Ashraf Ahmed
    Department Molecular Biology, Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
    Protein J 27:151-62. 2008
    ....
  13. ncbi request reprint Evaluation of a botulinum fragment C-based ELISA for measuring the humoral immune response in primates
    Changhong Y Lindsey
    Office of Product Development and Regulatory Affairs, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702 5011, USA
    Biologicals 31:17-24. 2003
    ....
  14. ncbi request reprint Botulinum neurotoxin vaccines: Past history and recent developments
    Janice M Rusnak
    Clinical Research Management, Inc, USA
    Hum Vaccin 5:794-805. 2009
    ..Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT...
  15. ncbi request reprint Inhibition of the protease activity of the light chain of type A botulinum neurotoxin by aqueous extract from stinging nettle (Urtica dioica) leaf
    Nizamettin Gul
    Department of Immunology and Molecular Biology, Division of Toxinology and Aerobiology, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702 5011, USA
    Basic Clin Pharmacol Toxicol 95:215-9. 2004
    ..The inhibition mode of water soluble fraction against protease activity of type A light chain was analyzed and found to be a non-competitive...
  16. ncbi request reprint Autocatalytically fragmented light chain of botulinum a neurotoxin is enzymatically active
    S Ashraf Ahmed
    Department of Immunology and Molecular Biology, Division of Toxinology and Aerobiology, U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Maryland 21702, USA
    Biochemistry 42:12539-49. 2003
    ..Our results of LC concentration dependence of the fragmentation reaction indicate that the autocatalysis occurs by both intramolecular and intermolecular mechanisms...
  17. doi request reprint Botulism: cause, effects, diagnosis, clinical and laboratory identification, and treatment modalities
    Zygmunt F Dembek
    US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Ft Detrick, MD 21702, USA
    Disaster Med Public Health Prep 1:122-34. 2007
    ..Due to declining immunogenicity and potency of the pentavalent botulinum toxoid, novel vaccine candidates are being developed...
  18. ncbi request reprint Factors affecting autocatalysis of botulinum A neurotoxin light chain
    S Ashraf Ahmed
    Department of Immunology and Molecular Biology, Division of Toxinology and Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
    Protein J 23:445-51. 2004
    ..Our results provide a choice of buffers and salts for isolation, purification and storage of intact botulinum neurotoxin serotype A light chain...
  19. ncbi request reprint EL4 cell-based colorimetric toxin neutralization activity assays for determination of neutralizing anti-ricin antibodies
    Changhong Y Lindsey
    United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA
    J AOAC Int 96:147-54. 2013
    ..The testing conditions were adjusted to optimize assay performance. The colorimetric TNA assay replaced a radioactive TNA assay previously used in the ricin vaccine studies...
  20. doi request reprint Extreme sensitivity of botulinum neurotoxin domains towards mild agitation
    Stephen I Toth
    Department Molecular Biology, Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702, USA
    J Pharm Sci 98:3302-11. 2009
    ..We speculate that the BoNT domains undergo surface denaturation due to rapid exposure of hydrophobic residues by mechanical agitation. This study has important implications for handling BoNT proteins used in therapeutic development...
  21. pmc Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4 and B1 strains: BoNT/A3, /Ba4 and /B1 clusters are located within plasmids
    Theresa J Smith
    Integrated Toxicology Division, United States Army Medical Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America
    PLoS ONE 2:e1271. 2007
    ..The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression...
  22. doi request reprint Production of catalytically inactive BoNT/A1 holoprotein and comparison with BoNT/A1 subunit vaccines against toxin subtypes A1, A2, and A3
    Robert P Webb
    United States Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, United States
    Vaccine 27:4490-7. 2009
    ..Differences in protective immunity diminished after multiple vaccinations with either ciBoNT/A1 HP or BoNT/A1 H(c), and the survival rates were more comparable at the toxin levels used to challenge...
  23. ncbi request reprint Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity
    John H Carra
    Integrated Toxicology Division, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702 5011, United States
    Vaccine 25:4149-58. 2007
    ..Our results suggest that optimization of adherence of a protein antigen to aluminum adjuvant can be a useful route to increasing both stability and effectiveness, and support a role for a "depot effect" of adjuvant...
  24. pmc The C terminus of the catalytic domain of type a botulinum neurotoxin may facilitate product release from the active site
    Rahman M Mizanur
    From the Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702
    J Biol Chem 288:24223-33. 2013
    ..Our results also underscore the importance of using a mature LcA as an inhibitor screening target. ..
  25. pmc Tyrosine phosphorylation of botulinum neurotoxin protease domains
    Stephen Toth
    Integrated Toxicology Division, Department of Biochemistry and Cell Biology, United States Army Medical Research Institute of Infectious Diseases Fort Detrick, MD, USA
    Front Pharmacol 3:102. 2012
    ..Inclusion of a competitive inhibitor protected Y426 of LcA from phosphorylation, shedding light on the role of the C-terminus in the enzyme's substrate or product binding...
  26. ncbi request reprint Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice
    John S Lee
    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
    Vaccine 24:6886-92. 2006
    ..These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases...
  27. ncbi request reprint Finding a new vaccine in the ricin protein fold
    Mark A Olson
    United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702 5011, USA
    Protein Eng Des Sel 17:391-7. 2004
    ..We conclude that comparative protein analysis and engineering yielded a superior vaccine by exploiting a component of the toxin that is inherently more stable than is the parent RTA molecule...
  28. ncbi request reprint N-terminal helix reorients in recombinant C-fragment of Clostridium botulinum type B
    Seetharaman Jayaraman
    Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
    Biochem Biophys Res Commun 330:97-103. 2005
    ..The probable reasons for different binding affinity of botulinum and tetanus toxins are discussed...
  29. ncbi request reprint Clostridium perfringens iota toxin. Mapping of the Ia domain involved in docking with Ib and cellular internalization
    Jean Christophe Marvaud
    CNR AnaƩrobies, Institut Pasteur, 75724 Paris Cedex 15, France
    J Biol Chem 277:43659-66. 2002
    ..These findings revealed that iota toxin is a suitable system for mediating the entry of heterologous proteins such as C3 into cells...
  30. pmc Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine
    Mingtao Zeng
    Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Vaccine 25:7540-8. 2007
    ..The data suggest that an adenovirus-vectored genetic vaccine is a highly efficient prophylaxis candidate against botulism...
  31. ncbi request reprint Bioterrorism: what level is the threat and are vaccines the answer?
    Leonard A Smith
    Expert Rev Vaccines 3:493-5. 2004
  32. ncbi request reprint Pichia pastoris fermentation with mixed-feeds of glycerol and methanol: growth kinetics and production improvement
    Wenhui Zhang
    Department of Chemical Engineering, University of Nebraska Lincoln, 207M Othmer Hall, Lincoln, NE 68583 0919, USA
    J Ind Microbiol Biotechnol 30:210-5. 2003
    ..The results show that the optimal desired micro (gly)/ micro (MeOH) is around 2 for obtaining the highest BoNT/C(Hc) protein content in cells: about 3 mg/g wet cells...
  33. ncbi request reprint Scale-up of the fermentation and purification of the recombinant heavy chain fragment C of botulinum neurotoxin serotype F, expressed in Pichia pastoris
    Scott K Johnson
    Biological Process and Development Facility, University of Nebraska Lincoln, Lincoln, NE 68583 0919, USA
    Protein Expr Purif 32:1-9. 2003
    ..The ratios of the two clipped forms were consistent from the bench to pilot scales. Purified BoNTF(Hc) at the pilot scale was found to sufficiently protect mice against a high dose of BoNTF neurotoxin...
  34. pmc Differentiation of Clostridium botulinum serotype A strains by multiple-locus variable-number tandem-repeat analysis
    Thomas E Macdonald
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Appl Environ Microbiol 74:875-82. 2008
    ..These markers provide clinical and forensics laboratories with a rapid, highly discriminatory tool to distinguish among C. botulinum BoNT/A1 strains for investigations of botulism outbreaks...
  35. ncbi request reprint Purification and scale-up of a recombinant heavy chain fragment C of botulinum neurotoxin serotype E in Pichia pastoris GS115
    Michael P Dux
    Biological Process Development Facility, Department of Chemical Engineering, University of Nebraska Lincoln, Lincoln, NE 68588 0466, USA
    Protein Expr Purif 45:359-67. 2006
    ..N-terminal sequencing showed that the purified rBoNTE(Hc) N-terminus is intact and was found to protect mice against a challenge of 1000 mouse intraperitoneal LD50's of BoNT/E...
  36. ncbi request reprint Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H(c)): antigen E) by Pichia pastoris
    Jayanta Sinha
    Biological Process Development Facility, Department of Chemical and Biomolecular Engineering, University of Nebraska Lincoln, Lincoln, NE 68588 0466, USA
    J Biotechnol 127:462-74. 2007
    ..The optimized process had an induction time of 9 h on methanol and produced up to 3 mg of rBoNTE(H(c)) per gram wet cell mass as determined by HPLC and Western blot analysis...
  37. ncbi request reprint Purification of the N- and C-terminal subdomains of recombinant heavy chain fragment C of botulinum neurotoxin serotype C
    Jicai Huang
    Department of Chemical Engineering, University of Nebraska, Lincoln, NE, USA
    Methods Mol Biol 389:77-98. 2007
    ....