[ Research Interests ] [ Representative Publications ]

Richard Cone Professor Department of Biology Department of Biophysics B.S. Massachussetts Institute of Technology M.S. University of Chicago Ph.D. University of Chicago

Department of Biophysics Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218-2685 U.S.A. Office Telephone: Lab Telephone: Department Fax: Email: 410.516.7259 410.516.6596 410.516.4118 cone@jhu.edu Jenkins Hall Office: Jenkins 320

Research Interests Our “Mucosal Protection Laboratory” is developing barrier methods for protecting against sexually transmitted diseases (STDs) and unwanted pregnancy, methods more appealing to use than condoms. Microbicides for this purpose must not only block the infectious entry of STD pathogens they must also be safe to use repeatedly on mucosal surfaces, and they must not disturb healthy microflora of the vagina (lactobacilli). Research in the Mucosal Protection Laboratory helped create “BufferGel”, a spermicidal microbicide now in major clinical efficacy trials (funded by NIH) for preventing HIV infections and for contraception. BufferGel’s basic mechanism of protection is quite simple: The vagina is mildly acidic (~pH 4), sufficiently acidic to protect against many types of pathogens. But sperm are acid-sensitive, so semen is alkaline and the ejaculate abolishes the protective acidity of the vagina for many hours after intercourse. Otherwise sperm would be killed within seconds by vaginal acidity. Unfortunately the alkalinizing action of semen helps acid-sensitive STD pathogens, not just sperm, to survive in the vagina. Acid sensitive STD pathogens include HIV, HSV, syphilis, and chlamydia. Since BufferGel can rapidly acidify semen it is expected to protect against both sperm and these acid-sensitive pathogens while not disturbing acid-tolerant vaginal lactobacilli. Research on BufferGel and other microbicides is being performed in part through an ongoing Research Agreement with ReProtect, Inc, the JHU-associated company that is pursuing commercial development of BufferGel. What is the most common vaginal infection? (It is more common than yeast infections.) The answer: Bacterial Vaginosis (“BV”). Most people have never heard of it, and it is asymptomatic in most women. Worldwide, it is estimated that 1 out of 4 women have BV. Even though most people don’t know about it, recent epidemiological studies have revealed that BV is a major health problem: Women with BV are at greatly increased risk of HIV and other STD infections, and BV greatly increases the risk of stillbirths, premature births, and pelvic and perinatal infections. During a BV infection, the lactobacilli die off, the pH of the vagina rises, and a marked polymicrobial overgrowth occurs, coating every epithelial cell with a carpet of bacteria. Our research suggests that BufferGel will help prevent BV, and the ongoing clinical trials will determine whether or not it does. In the meantime our lab is investigating what causes BV and the mechanisms by which BV might increase the risk of HIV and other STD infections. Little is known about what causes BV, and no one knows how it is transmitted, so we are embarking on several foundation-building research projects that use simple microbiology techniques. The first graduate student to pursue research on BV in the Mucosal Protection Lab was Elizabeth Boskey. She chose to investigate the question: “What makes the vagina acidic?” For over 100 years many clinicians have thought that the vagina is probably acidified by the lactic acid produced by lactobacilli, but no one actually tested whether or not this hypothesis was correct. More recently, some clinicians suggested another reasonable hypothesis is that since the vagina is anaerobic, anaerobic metabolism by the epithelial cells produces most of the lactic acid. Boskey’s thesis research provided the first definitive evidence that vaginal acidity is in fact produced primarily by lactobacilli, not by the vaginal epithelium (see Boskey et al, 2001). We are now investigating how the lactic acid produced by vaginal lactobacilli inhibits the growth of BV-associated microbes. Representative Publications Cone, R.A, Hoen, T., Wong, X., Abusuwwa, R., Anderson, D.J., and Moench, T.R. 2006. Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission. BMC Infect Dis. 6:90. Lai, S. K., O'Hanlon, D.E., Harrold, S., Man, S.T., Wang, Y.Y., Cone, R., Hanes J. 2007. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci U S A. 104:1482-7. Boskey ER, Moench TR, Hees PS, Cone RA. 2003. A self-sampling method to obtain large volumes of undiluted cervicovaginal secretions. Sex Transm Dis.Feb;30(2):107-9. Achilles SL, Shete PB, Whaley KJ, Moench TR, Cone RA. 2002. Microbicide efficacy and toxicity tests in a mouse model for vaginal transmission of Chlamydia trachomatis. Sex Transm Dis. 29(11):655-64. Castle PE, Karp DA, Zeitlin L, Garcia-Moreno E B, Moench TR, Whaley KJ, Cone RA. 2002. Human monoclonal antibody stability and activity at vaginal pH. J Reprod Immunol. 56(1-2):61-76. Khanna KV, Whaley KJ, Zeitlin L, Moench TR, Mehrazar K, Cone RA, Liao Z, Hildreth JE, Hoen TE, Shultz L, Markham RB. 2002. Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent. J Clin Invest. Jan;109(2):205-11. Boskey E.R., R.A. Cone, K.J. Whaley, and T.R. Moench. 2001. Origin of vaginal acidity: High D/L lactate ratio is consistent with bacteria being the primary source. Hum. Reprod., 16:1809-1813. Olmsted, S.S., J.L. Padgett, A.I. Yudin, K.J. Whaley, T.R. Moench, and R.A. Cone. 2001. Diffusion of macromolecules and virus-sized-particles in human cervical mucus. Biophys. J. 81:1930-1937. Cone, R.A. 1999. Mucus. In Handbook of mucosal immunology, Second Edition, ed. by Ogra, Mestecky, Lamm, McGhee, and Bienenstock, 43-64. San Diego: Academic Press. Castle, P.E., K.J. Whaley, T.E. Hoen, T.R. Moench, and R.A. Cone. 1997. Contraceptive effect of sperm-agglutinating monoclonal antibodies in rabbits. Biol. of Reprod. 56:153-159. Cone, R.A., and K.J. Whaley. 1994. Monoclonal antibodies for reproductive health: Preventing sexual transmission of disease and pregnancy with topically applied antibodies. Am. J. Reprod. Immunol. 32/2:114-131.

Johns Hopkins University
3400 N. Charles St.
Baltimore, MD 21218

E-mail updates to the CMDB Webmaster