Brichacek B, Lagenaur, LA, Lee, PP, Venzon, D, Hamer, DH. PLoS One. 2013 Nov 12;8(11):e78817. doi: 10.1371/journal.pone.0078817.



Synopsis: A preclinical safety study was performed in macaques colonized with Lactobacillus jensenii engineered to secrete modified cyanovirin-N (mCV-N). The following biomarkers [G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL12/23(p-40), IL-13, IL-15, IL-17, MCP-1, MIP-1β, MIP-1α, sCD40L, TGFα,TNFα, VEGF, and IL-18] were measured in cervical vaginal lavage and plasma from macaques before and during colonization using luminex technology. The L. jensenii producing mCV-N appeared to be safe and did not elicit any pro-inflammatory immune responses in the vaginal mucosa. IL-13, a mediator of allergic inflammation, was detectable in the CVL of 7/8 control macaques, but was only detectable in 3/12 CVLs from LB-mCV-N colonized macaques. In macaques that were dosed repeatedly with LB-mCV-N and challenged with SHIV, IL-1RA was found to be upregulated in CVLs compared to the levels in CVLs of controls (p=0.013), and interesting was predictive of lower viral load in macaques with breakthrough infection.