Lactobacilli-expressed single-chain variable fragment (scFv) specific for intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1 transmission across a cervical epithelial monolayer

Caren J. Chancey, Kristen V. Khanna, Jos F M L Seegers, Guang Wen Zhang, James Hildreth, Abigail Langan, Richard B. Markham

Research output: Contribution to journalArticle

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Abstract

The vaginal and cervical epithelia provide an initial barrier to sexually acquired HIV-1 infection in women. To study the interactions between HIV-1-infected cells or cell-free HIV-1 and the reproductive epithelium, the transmission of HIV-1 by infected cells or cell-free virus across human cervical epithelial cells was examined using a Transwell culture system. Cell-associated HIV-1 was transmitted more efficiently than cell-free virus, and monocyte-associated virus was transmitted most efficiently. Abs to ICAM-1 added to the apical side of the epithelium blocked cell-mediated transepithelial HIV-1 transmission in vitro. When used in a previously described model of vaginal HIV-1 transmission in human PBL-SCID mice, anti-murine ICAM-1 Abs (0.4 μg/10 μl) also blocked vaginal transmission of cell-associated HIV-1 in vivo. To evaluate a candidate delivery system for the use of this Ab as an anti-HIV-1 microbicide, anti-ICAM single-chain variable fragment Abs secreted by transformed lactobacilli were evaluated for their protective efficacy in the Transwell model. Like the intact Ab and Fab derived from it, the single-chain variable fragment at a concentration of 6.7 μg/100 μl was able to reduce HIV-1 transmission by 70 ± 5%. These data support the potential efficacy of an anti-ICAM Ab delivered by lactobacilli for use as an anti-HIV-1 microbicide.

Original languageEnglish (US)
Pages (from-to)5627-5636
Number of pages10
JournalJournal of Immunology
Volume176
Issue number9
StatePublished - May 1 2006
Externally publishedYes

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Single-Chain Antibodies
Lactobacillus
Intercellular Adhesion Molecule-1
HIV-1
Epithelium
Anti-Infective Agents
Viruses
Satellite Viruses
SCID Mice
HIV Infections
Monocytes
Epithelial Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Lactobacilli-expressed single-chain variable fragment (scFv) specific for intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1 transmission across a cervical epithelial monolayer. / Chancey, Caren J.; Khanna, Kristen V.; Seegers, Jos F M L; Zhang, Guang Wen; Hildreth, James; Langan, Abigail; Markham, Richard B.

In: Journal of Immunology, Vol. 176, No. 9, 01.05.2006, p. 5627-5636.

Research output: Contribution to journalArticle

Chancey, Caren J. ; Khanna, Kristen V. ; Seegers, Jos F M L ; Zhang, Guang Wen ; Hildreth, James ; Langan, Abigail ; Markham, Richard B. / Lactobacilli-expressed single-chain variable fragment (scFv) specific for intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1 transmission across a cervical epithelial monolayer. In: Journal of Immunology. 2006 ; Vol. 176, No. 9. pp. 5627-5636.
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abstract = "The vaginal and cervical epithelia provide an initial barrier to sexually acquired HIV-1 infection in women. To study the interactions between HIV-1-infected cells or cell-free HIV-1 and the reproductive epithelium, the transmission of HIV-1 by infected cells or cell-free virus across human cervical epithelial cells was examined using a Transwell culture system. Cell-associated HIV-1 was transmitted more efficiently than cell-free virus, and monocyte-associated virus was transmitted most efficiently. Abs to ICAM-1 added to the apical side of the epithelium blocked cell-mediated transepithelial HIV-1 transmission in vitro. When used in a previously described model of vaginal HIV-1 transmission in human PBL-SCID mice, anti-murine ICAM-1 Abs (0.4 μg/10 μl) also blocked vaginal transmission of cell-associated HIV-1 in vivo. To evaluate a candidate delivery system for the use of this Ab as an anti-HIV-1 microbicide, anti-ICAM single-chain variable fragment Abs secreted by transformed lactobacilli were evaluated for their protective efficacy in the Transwell model. Like the intact Ab and Fab derived from it, the single-chain variable fragment at a concentration of 6.7 μg/100 μl was able to reduce HIV-1 transmission by 70 ± 5{\%}. These data support the potential efficacy of an anti-ICAM Ab delivered by lactobacilli for use as an anti-HIV-1 microbicide.",
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