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PREVENTION OF VAGINAL SHIV TRANSMISSION IN MACAQUES BY A LIVE RECOMBINANT LACTOBACILLUS.

Lagenaur1,2, L.A., Sanders-Beer3, B.E., Brichacek1, B., Pal4, R., Liu2, X. Liu2, Y., Yu5, R., Venzon6, D., Lee2, P.P., and Hamer1, D.H.  1Gene Structure and Regulation Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 2Osel, Mountain View, California, USA. 3BIOQUAL, Rockville, Maryland, USA. 4Advanced BioScience Laboratories, Rockville, Maryland, USA. 5Cepheid, Sunnyvale, California, USA. 6Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA.
Abstract

Most human immunodeficiency virus (HIV) transmissions in women occur through the cervicovaginal mucosa, which is coated by a bacterial biofilm including Lactobacillus . This commensal bacterium has a role in maintaining a healthy mucosa and can be genetically engineered to produce antiviral peptides. Here, we report a 63 % reduction in transmission of a chimeric simian / HIV (SHIVSF162P3) after repeated vaginal challenges of macaques treated with Lactobacillus jensenii expressing the HIV-1 entry inhibitor cyanovirin-N. Furthermore, peak viral loads in colonized macaques with breakthrough infection were reduced sixfold. Colonization and prolonged antiviral protein secretion by the genetically engineered lactobacilli did not cause any increase in proinflammatory markers. These findings lay the foundation for an accessible and durable approach to reduce heterosexual transmission of HIV in women, which is coitally independent, inexpensive, and enhances the natural protective effects of the vaginal microflora.

Keywords

Antiviral peptides, Cervicovaginal mucosa, Entry inhibitor, EpiVaginal, HIV transmission, Macaques, VLC-100 FT

Materials Tested

CV-N, Cyanovirin-N (CV-N), HIV-1, Human immunodeficiency virus-1, Lactobacillus, Lactobacillus jensenii

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