Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus

• Published in: Mucosal immunology Vol. 4; no. 6; pp. 648 - 657
• Main Authors: Lagenaur, L A, Sanders-Beer, B E, Brichacek, B, Pal, R, Liu, X, Liu, Y, Yu, R, Venzon, D, Lee, P P, Hamer, D H
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-11-2011; Elsevier Limited
• Subjects: 631/250/347; 631/326/41; 631/326/596/2563; Administration, Intravaginal; Allergology; Animals; Antibodies; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Biomedicine; Carrier Proteins - genetics; Carrier Proteins - immunology; Carrier Proteins - metabolism; Cytokines - blood; Disease Models, Animal; Female; Gastroenterology; Genetic Engineering; HIV - genetics; HIV - immunology; HIV - pathogenicity; HIV Infections - immunology; HIV Infections - microbiology; HIV Infections - transmission; Humans; Immunity, Mucosal - genetics; Immunology; Lactobacillus - genetics; Lactobacillus - growth & development; Lactobacillus - immunology; Lactobacillus - metabolism; Macaca mulatta; Recombinant Fusion Proteins - genetics; Simian Immunodeficiency Virus - genetics; Vagina - immunology; Vagina - metabolism; Vagina - microbiology; Viral Load; Virus Internalization
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2011.30

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 (SHIV
SF162P3
) 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.