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.
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 microg/10 microl) 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 microg/100 microl 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.
Chancey
Caren J
CJ
Johns Hopkins Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Khanna
Kristen V
KV
Seegers
Jos F M L
JF
Zhang
Guang Wen
GW
Hildreth
James
J
Langan
Abigail
A
Markham
Richard B
RB
D000818:Animals; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007778:Lactobacillus / Q000276:immunology*; D051379:Mice; D009000:Monocytes; D013997:Time Factors
D007141:Immunoglobulin Fc Fragments; D018799:Intercellular Adhesion Molecule-1