title: Development of a topical vaginal microbicide: lessons learned from human milk.
abstract: Vaccines are not presently available to prevent adherence and transmission of many common pathogens at mucosal surfaces. As a result, sexually transmitted diseases were one of the most commonly reported infections in the US in 1999. New methods are needed to reduce the spread of mucosal infections. Providing nonspecific protective factors, such as lipids and retinoids found in human milk to mucosal surfaces could reduce mucosal infection caused by viruses, e.g., herpes simplex virus-1 (HSV-1) and bacteria, e.g., Pseudomonas aeruginosa. Human milk lipids enzymatically modified to produce monoglycerides were antimicrobial and inactivated enveloped viruses, as well as gram-positive and gram-negative bacteria. Enveloped viruses were inactivated in seconds following contact with antimicrobial lipids, and P. aeruginosa infectivity was reduced by 99.9% after 2 hours. Transmission of pathogens at mucosal surfaces can also be prevented using retinoids that inhibit viral replication. In a human embryonic intestinal cell line the retinoic acid (RA) derivatives all-trans-RA and 9-cis-RA (10 microg/mL) decreased the production of HSV-1 and Echo-6 viruses by 1-2 log10 over a 48-hour period. In addition, all-trans-RA inhibited HSV-1 replication in Vero cells as effectively as interferon beta, reducing viral production by 2.5log10. These studies indicate that lipids and retinoids could be part of a topical microbicide to prevent mucosal infections.
authors.affiliation: Department of Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Isaacs
authors.forename: R
authors.initials: R
authors.lastname: Pullarkat
authors.forename: R
authors.initials: R
authors.lastname: Kascsak
mesh_terms: D000891:Anti-Infective Agents, Local; D000998:Antiviral Agents / Q000627:therapeutic use; D036861:Delivery, Obstetric; D005260:Female; D006801:Humans; D007239:Infections / Q000635:transmission*; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000737:chemistry*; D012749:Sexually Transmitted Diseases / Q000635:transmission; D014212:Tretinoin / Q000627:therapeutic use; D014623:Vaginal Diseases / Q000382:microbiology* / Q000469:parasitology; D016585:Vaginosis, Bacterial / Q000517:prevention & control / Q000635:transmission; D014777:Virus Diseases / Q000517:prevention & control / Q000635:transmission
chemical_list: D000891:Anti-Infective Agents, Local; D000998:Antiviral Agents; D014212:Tretinoin