Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge

Abstract

Measures to prevent sexual mucosal transmission are critically needed, particularly to prevent transmission to young women at high risk in the microepidemics in South Africa that disproportionally contribute to the continued pandemic. To that end, microbicides containing anti-retroviral (ARV) agents have been shown to prevent transmission, but with efficacy limited both by adherence and pre-existing innate immune and inflammatory conditions in the female reproductive tract (FRT). Glycerol monolaurate (GML) has been proposed as a microbicide component to enhance efficacy by blocking these transmission-facilitating innate immune response to vaginal exposure. We show here in an especially rigorous test of protection in the SIV-rhesus macaque model of HIV-1 transmission to women, that GML used daily and before vaginal challenge protects against repeat high doses of SIV by criteria that include virological and immunological assays to detect occult infection. We also provide evidence for indirect mechanisms of action in GML-mediated protection. Developing a sustained formulation for GML delivery could contribute an independent, complementary protective component to an ARV-containing microbicide.

Coconut (Cocos nucifera)

“…This viral disease affects 7.2 million people in Asian and Pacific countries, while India is reported to have 3.5-5.0 million sufferers. Its modes of action were thought to include membrane stabilization including its microbicide activity-ie, blocking bacterial pore-forming toxins and T-cell activation, as well as blocking expression of the signaling pathway that leads to establishment of infected T-cells (Haase et al, 2015). Monolaurin derived from coconut oil has virucidal effects on RNA and DNA viruses that are surrounded by a lipid membrane, including HIV.…”

Characterizing how glycerol monolaurate (GML) affects human T cell signaling and function

“…GML also has antiviral activity against enveloped viruses such as Cytomegalovirus (CMV) in vitro [136]. Topical gel formulated GML in the vaginal mucosa of Rhesus Macaques decreases SIV viremia in a vaginal challenge of Simian Immunodeficiency Virus (SIV) in vivo [137,138]. The above findings…”

“…At GML concentrations that are antimicrobial, GML does not result in cytotoxicity for human gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells [141]. However GML incorporated into tampons and GML infused gels applied topically in the vagina result in decreased IL-8 in the vaginal environment [130,138], suggesting that GML has an immunomodulatory role. Furthermore, GML treated T cells have decreased cellular proliferation when stimulated with phorbol 12-myristate 12-acetate (PMA), concanavalin A (ConA), and TSST-1 [142].…”

“…It is also widely available as a homeopathic supplement, and is extensively used as a food preservative and emulsifier [123,124]. Topical GML is being tested as a treatment and/or preventative measure for Toxic Shock Syndrome, HIV transmission, and surgical site infections [130,138,160]. Thus, GML is an effective antimicrobial that comes in regular contact with the general public through its extensive commercial and therapeutic uses.…”

“…10 Glycerol monolaurate (GML) is a widely used fatty acid molecule that also has potent antimicrobial properties [126,129,133,136,137]. Because of this, topical GML is currently being tested as a therapeutic for Toxic Shock Syndrome, HIV transmission, and surgical site infections [130,138,160]. Interestingly, in addition to being an antimicrobial, GML also suppresses T cell activation induced events.…”