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New drugs can treat mucosal damage caused by HIV infection
Medical Network May 10, vaginal fungicides can prevent the sexual transmission of HIV-1 in women, with great potential to save lives and help stop the epidemic. However, the delicate environment of microbes naturally settles in the vagina and maintains a healthy mucosal barrier, making the search for such microbicides challenging and hindering the development of clinical trials.
Researchers at the Brigham and Women's Hospital , led by Dr. Raina Fichorova, tested a laboratory-produced natural protein (recombinant fragment of human surfactant protein D or rfhSP-D), immune cells and microbes on bioengineered vaginal tissue. To determine if a drug candidate can help prevent HIV transmission safely. The team's work in Frontiers in Immunology reported the success of the technology in preclinical testing and established it as a promising anti-HIV-1 vaginal bactericide.
“To find a new drug that can most effectively help the immune system without adverse reactions is a daunting task that requires a basic understanding of mucosal ecosystems and Biotechnology knowledge,†said Brigham Labs Director. Dr. Raina Fichorova, MD, MD, said: "Our team is able to combine the expertise of these two areas to carry out this work and lay a solid foundation for rfhSP-D as a clinical trial for topical anti-HIV fungicides."
The team designed a sexually transmitted model of HIV transmission through bioengineering, multi-layered vaginal tissue to the underlying white blood cells. Two major events often lead to HIV infiltration and spread: inflammation and destruction of the mucosal barrier. The research team first reported the genetic signature associated with this violation. In the presence of a virus, the activity of the genes involved in inflammation and the tightness of the barrier are altered to help promote infection.
Fichorova and colleagues found that the drug candidate rfhSP-D not only prevented HIV transmission, but also reversed the genetic characteristics of vaginal tissue in the presence of the virus. This molecule helps maintain the integrity of the vaginal tissue and inhibits the pro-inflammatory response, preventing the virus from gaining a foothold. In addition, a number of preclinical tests have shown that the molecule can be safely applied without altering naturally occurring bacteria such as lactobacilli or destroying the vaginal mucosa.
“Our research provides a highly reproducible, cost-effective model for studying the effectiveness of candidate microbicides. Our findings provide a strong assessment of rfhSP-D as a potential topical anti-HIV biocide. Argument." (Bio Valley Bioon.com)
Information source: Drug candidate for reversing mucosal barrier damage by HIV
Original source: Hrishikesh Pandit, Kavita Kale, Hidemi Yamamoto, Gargi Thakur, Sushama Rokade, Payal Chakraborty, Madavan Vasudevan, Uday Kishore, Taruna Madan, Raina Nakova Fichorova. Surfactant Protein D Reverses the Gene Signature of Transepithelial HIV-1 Passage and Restricts the Viral Transfer Across the Vaginal Barrier. Frontiers in Immunology, 2019; 10 DOI: 10.3389/fimmu.2019.00264