Volume 3 Supplement 1

2006 International Meeting of The Institute of Human Virology

Open Access

Live microbial microbicides for HIV

  • Dean Hamer1,
  • Louise McHugh1,
  • Margaret McKinney1,
  • Chris Richards1,
  • Kevin Schully1,
  • Laurel Lagenaur2 and
  • Srinivas Rao3
Retrovirology20063(Suppl 1):S50

https://doi.org/10.1186/1742-4690-3-S1-S50

Published: 21 December 2006

Background

Most HIV transmission occurs on the mucosal surfaces of the gastrointestinal and cervico-vaginal tracts, which are coated by a biofilm of commensal bacteria. We are genetically engineering such naturally occurring bacteria to secrete peptides that block viral infection or replication. Introduction of such genetically modified organisms into uninfected individuals under conditions where they colonize the mucosa would provide a long lasting bioshield against HIV.

Materials and methods

Nissle 1917, a highly colonizing probiotic strain of E. coli, was genetically engineered to secrete an HIV fusion-blocking peptide through the hemolysin A secretion pathway. Lactobacillus jensenii 1153, a natural vaginal isolate, was modified to secrete the same peptide via the S-protein layer secretion pathway.

Results

By using a combination of cis- and trans-acting regulatory signals, micromolar secretion levels of the anti-HIV peptide were achieved in Nissle 1917. In vitro the genetically engineered E. coli potently blocked infection of T cells and macrophage by a wide spectrum of HIV primary isolates. In vivo, the modified strain colonized the lower intestine of rhesus macaques, and protected 50% of animals against rectal infection by pathogenic SHIV162p3 in a small cohort of animals challenged shortly following colonization. Genetically engineered L. jensenii also secreted fusion-inhibitor peptide and colonized the vagina in estrus phase mice and in macaques.

Conclusion

Our data demonstrate the potential of genetically modified commensal bacteria to provide cheap, effective protection against HIV infection.

Authors’ Affiliations

(1)
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health
(2)
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases and Osel, Inc.
(3)
Vaccine Research Center, National Institutes of Health

Copyright

© Hamer et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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