Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4

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 majority of anti-HIV-1 microbicides currently in development target cell-free virus transmission and viral epitopes, although host cell epitopes including CD4 and CCR5 have been targeted with some success (54,55). Anti-ICAM-1 has the advantage of targeting a conserved host epitope that is not subject to the variability of viral epitopes.…”

“…Lactobacillus-produced scFvs have been shown to be effective in a variety of settings; purified soluble two-domain CD4 molecules expressed by engineered lactobacilli have reduced HIV-1 infectivity in an in vitro model, and scFvs secreted by engineered lactobacilli in situ have reduced dental caries caused by Streptococcus mutans in vivo (54,58). An advantage of this system for microbicidal applications is that lactobacilli are Gram-positive commensal bacteria commonly found as part of the normal microflora of the female genitourinary tract.…”

Genetically Engineered Lactobacilli for Technological and Functional Food Applications

“…In this sense a vector has been recently developed that contains a bile salt hydrolase gene from L. plantarum and which allows the host to grow in media containing bile salts (Yin et al, 2011). Bioluminiscence markers have also been used in lactobacilli and they are based on genes encoding enzymes that produce light as lux, which encodes bacterial luciferase, and gfp that encodes green fluorescence protein (Chang et al, 2003;Perez-Arellano & Perez-Martinez, 2003). …”

Reducing Urogenital Infections Including HIV in Sub-Saharan Africa - Can Probiotics Be a Viable Paradigm?

“…The work provides proof of principle for the use of some Lactobacilli, notably L. jensenii-produced C1C5 RANTES to block HIV-1 infection of CD4 T cells and macrophages, setting the basis for the development of a live anti-HIV-1 microbicide targeting CCR5 in an antagonistic manner [Luca et al 2010] Other studies have previously used Lactobacilli and other probiotic genetically modified bacteria to produce specific HIV inhibitory proteins, both membrane-bound and secreted. A strain of L. jensenii was engineered to produce functional CD4, the primary receptor for HIV [Chang et al, 2003]. There are several classes of proteins that bind to the mannose residues of HIV, including a unique 11 kd protein from cyanobacteria (Nostoc ellipsosporum) called cyanovirin-N and mannose-binding lectins which also bind to Neisseria gonorrhoeae [Botos & Wlodawer, 2005 ] .An E. coli strain which colonizes the colon and rectum, and may thus potentially prevent anal transmission, has been modified to secrete peptides hybridized with hemolysin A, a protein that can complex with the HIV fusion protein gp41 [Rao et al 2005].…”