1887

Journal of Medical Microbiology logo

Volume 61, Issue 9

Infecting mice with recombinant Ad5-BPI-Fcγ1 virus protects against systemic challenge Free

Abstract

Infections caused by Gram-negative bacteria (GNB) are increasingly common and can result in significant mortality rates due to the development of sepsis. To examine the potential usage of a recombinant Ad5-BPI-Fcγ1 virus as a biological treatment against systemic infection by GNB, a construct containing the human bactericidal/permeability increasing protein (BPI) gene, encoding the functional N terminus (amino acid residues 1–199) of human BPI, and the Fcγ1 gene, encoding the Fc segment of human immunoglobulin G1, was inserted into an adenovirus serotype 5 (Ad5) chromosome to produce a recombinant Ad5-BPI-Fcγ1 virus. Human A549 cells in culture and BALB/c mice were infected with the recombinant Ad5-BPI-Fcγ1 virus and BPI-Fcγ1 expression was confirmed by Western blot analysis and ELISA. The concentrations of BPI-Fcγ1 protein were 5.59 µg ml and 21.37 ng ml and it was observed that these concentrations were sufficient to decrease endotoxin concentrations while enhancing bactericidal activity. In addition, mice treated with the recombinant Ad5-BPI-Fcγ1 virus had decreased levels of IL-1β and TNF-α and were protected from an O111 : B4 challenge. Our data support the concept that Ad5-mediated BPI-Fcγ1 gene delivery could be used as an ancillary biological treatment in the management of infection caused by GNB.

  • Received:
  • Accepted:
  • Published Online:
© 2012 SGM
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.040907-0
2012-09-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jmm/61/9/1262.html?itemId=/content/journal/jmm/10.1099/jmm.0.040907-0&mimeType=html&fmt=ahah

References

  1. Alexander S., Bramson J., Foley R., Xing Z. 2004; Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein. Blood 103:93–99 [View Article][PubMed]
     [Google Scholar]
  2. An Y. Q., Guan Y. Z., Ke Y., Yang G. Z. 2002; Construction, expression and biological assessment of BPI23-Fcγ1 recombinant protein prokaryotic expression vector. Chin Med Sci J 17:140–147[PubMed]
     [Google Scholar]
  3. Balk R. A. 2000; Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin 16:179–192 [View Article][PubMed]
     [Google Scholar]
  4. Beamer L. 2002; Human BPI: one protein’s journey from lab into clinical trials. ASM News 68:543–548
     [Google Scholar]
  5. Chart H., Smith H. R., La Ragione R. M., Woodward M. J. 2000; An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5α and EQ1. J Appl Microbiol 89:1048–1058 [View Article][PubMed]
     [Google Scholar]
  6. Chen J., Li C., Guan Y., Kong Q., Li C., Guo X., Chen Q., Jing X., Lv Z., An Y. 2007; Protection of mice from lethal Escherichia coli infection by chimeric human bactericidal/permeability-increasing protein and immunoglobulin G1 Fc gene delivery. Antimicrob Agents Chemother 51:724–731 [View Article][PubMed]
     [Google Scholar]
  7. Elsbach P., Weiss J. 1998; Role of the bactericidal/permeability-increasing protein in host defence. Curr Opin Immunol 10:45–49 [View Article][PubMed]
     [Google Scholar]
  8. Giroir B. P., Quint P. A., Barton P., Kirsch E. A., Kitchen L., Goldstein B., Nelson B. J., Wedel N. J., Carroll S. F., Scannon P. J. 1997; Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet 350:1439–1443 [View Article][PubMed]
     [Google Scholar]
  9. Giroir B. P., Scannon P. J., Levin M. 2001; Bactericidal/permeability-increasing protein – lessons learned from the phase III, randomized, clinical trial of rBPI21 for adjunctive treatment of children with severe meningococcemia. Crit Care Med 29:S130–S135 [View Article]
     [Google Scholar]
  10. Gray P. W., Flaggs G., Leong S. R., Gumina R. J., Weiss J., Ooi C. E., Elsbach P. 1989; Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations. J Biol Chem 264:9505–9509[PubMed]
     [Google Scholar]
  11. Havenga M. J., Vogels R., Bout A. 2001; Prospects for chimeric adenoviruses. IDrugs 4:179–188[PubMed]
     [Google Scholar]
  12. Jenssen H., Hamill P., Hancock R. E. W. 2006; Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511 [View Article][PubMed]
     [Google Scholar]
  13. Lazaron V., Barke R. A. 1999; Gram-negative bacterial sepsis and the sepsis syndrome. Urol Clin North Am 26:687–699 [View Article][PubMed]
     [Google Scholar]
  14. Li C., Li J., Lv Z., Guo X., Chen Q., Kong Q., An Y. 2006; Protection of mice from lethal endotoxemia by chimeric human BPI-Fc γ1 gene delivery. Cell Mol Immunol 3:221–225
     [Google Scholar]
  15. Martin G. S., Mannino D. M., Eaton S., Moss M. 2003; The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554 [View Article][PubMed]
     [Google Scholar]
  16. Nayak S., Herzog R. W. 2010; Progress and prospects: immune responses to viral vectors. Gene Ther 17:295–304 [View Article][PubMed]
     [Google Scholar]
  17. Nwanegbo E., Vardas E., Gao W., Whittle H., Sun H., Rowe D., Robbins P. D., Gambotto A. 2004; Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin Diagn Lab Immunol 11:351–357[PubMed]
     [Google Scholar]
  18. Obayashi T., Kawai T., Tamura H., Nakahara C. 1982; New limulus amoebocyte lysate test for endotoxaemia. Lancet 319:289 [View Article][PubMed]
     [Google Scholar]
  19. Raetz C. R. H. 1990; Biochemistry of endotoxins. Annu Rev Biochem 59:129–170 [View Article][PubMed]
     [Google Scholar]
  20. Raetz C. R., Whitfield C. 2002; Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700 [View Article][PubMed]
     [Google Scholar]
  21. Russo T. A., Mylotte D. 1998; Expression of the K54 and O4 specific antigen has opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate of E. coli . FEMS Microbiol Lett 162:311–315 [CrossRef]
     [Google Scholar]
  22. Tomanin R., Scarpa M. 2004; Why do we need new gene therapy viral vectors? Characteristics, limitations and future perspectives of viral vector transduction. Curr Gene Ther 4:357–372[PubMed] [CrossRef]
     [Google Scholar]
  23. Wang Y., Huang S., Sah V. P., Ross J. Jr, Brown J. H., Han J., Chien K. R. 1998; Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem 273:2161–2168 [View Article][PubMed]
     [Google Scholar]
  24. Weiss J., Olsson I. 1987; Cellular and subcellular localization of the bactericidal/permeability-increasing protein of neutrophils. Blood 69:652–659[PubMed]
     [Google Scholar]
  25. Weiss J., Elsbach P., Olsson I., Odeberg H. 1978; Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 253:2664–2672[PubMed]
     [Google Scholar]
  26. Xuefang J., Yunqing A., Guizhen Y. 2002; Effects on the expression and rennaturation of BPI23-Fcr1 recombinant bactericidal protein by site-directed mutagenesis. Chin J Microbiol Immunol 4:13–16
     [Google Scholar]
  27. Yamaguchi T., Kawabata K., Koizumi N., Sakurai F., Nakashima K., Sakurai H., Sasaki T., Okada N., Yamanishi K., Mizuguchi H. 2007; Role of MyD88 and TLR9 in the innate immune response elicited by serotype 5 adenoviral vectors. Hum Gene Ther 18:753–762 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.040907-0
Loading
Infecting mice with recombinant Ad5-BPI23-Fcγ1 virus protects against systemic Escherichia coli challenge
J. Med. Microbiol. 61, 1262 (2012); https://doi.org/10.1099/jmm.0.040907-0
/content/journal/jmm/10.1099/jmm.0.040907-0
/content/journal/jmm/10.1099/jmm.0.040907-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error