Results of a recent animal study offer new optimism for microbicides, biomedical products being developed to protect people against sexually transmitted infections (STIs), including HIV. Population Council scientists and their partners have found that a proprietary microbicide gel developed by the Council is safe, stable, and can prevent the transmission of HIV, herpes simplex virus 2 (HSV-2), and human papillomavirus (HPV), in both the vagina and rectum in animals. It has a window of efficacy in the vagina against all three viruses of at least eight hours prior to exposure. An in vitro study also provides the first data that the gel is effective against multiple strains of HIV.
The gel, known as MZC, contains MIV-150, zinc acetate, and carrageenan. MIV-150 and zinc acetate are potent antiviral agents that inhibit HIV via different mechanisms of action. MIV-150 is an enzyme inhibitor that blocks an early step of HIV replication in target cells, and zinc acetate is an antiviral agent with demonstrated activity against HIV and HSV-2. These compounds are mixed in a water-based solution of carrageenan, a compound derived from seaweed that has been shown to have potent activity against HPV. Infection with HSV-2 or HPV is associated with increased risk of HIV infection. Researchers believe that microbicides that target HIV, HSV-2, and HPV may more effectively limit HIV transmission than those that target HIV alone.
In this study, Council scientists and their partners used macaque and mouse models to examine whether MZC gel could prevent vaginal and rectal transmission of SHIV-RT (a virus combining genes from HIV and SIV, the monkey version of HIV), HSV-2, and HPV. They found that MZC:
- protected macaques against vaginal SHIV-RT infection when applied up to 8 hours prior to challenge
- protected macaques against rectal SHIV-RT infection when used close to the time of viral challenge
- protected mice against HSV-2 infection when applied vaginally or anally/rectally just before a high dose of virus
- protected mice against HSV-2 when applied between 8 hours before and 4 hours after vaginal challenge with a low dose of HSV-2
- protected mice against HPV when applied up to 24 hours before and 2 hours after vaginal challenge and also if applied 2 hours before or after HPV inoculation of the anus/rectum
Researchers involved in developing MZC described the results of the preclinical study as particularly encouraging because of the product’s broad spectrum of activity. According to José A. Fernández-Romero, a scientist at the Population Council and corresponding author of the paper, “It is the versatility of MZC that makes it a desirable microbicide candidate. It is effective against multiple viruses, can be used in both the vagina and the rectum, and retains its efficacy in the vagina over an extended period of time.”
Some microbicides are being designed as vaginal products for women, and others as rectal products for either men or women. Several candidate microbicides have been developed and tested over the past two decades. Turning the concept into reality has proved difficult, however. To date, no product has advanced beyond clinical trials in humans to regulatory approval.
The study was designed to establish proof of concept in monkeys and mice before taking steps to test in humans. Preclinical testing in animals is required by the FDA and is important to ensure the highest level of safety and to build the evidence base for potential efficacy in humans. Phase 1 safety trials of the gel in humans are now underway.
“In addition to the gel,” said Fernández-Romero, “we are exploring sustained-release intravaginal rings and on-demand nanofiber-based delivery systems for MZC.” He stressed that developing different delivery systems for effective medications is an important step in ensuring the ultimate success of any microbicide, adding, “There is a growing demand for microbicides that prevent multiple STIs, and we are committed to ensuring that women and men have options when choosing what works most effectively for their own protection.”
Kizima, Larisa, Aixa Rodríguez, Jessica Kenney, Nina Derby, Olfa Mizenina, et al. 2014. “A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV,” PLoS ONE 9(4): e94547. doi:10.1371/journal.pone.0094547
US Agency for International Development (USAID)