Grant: Operating Grant

Women's susceptibility to HIV infection via male-to-female transmission is in part due to the fact that current preventative methods such as abstinence, condoms, and monogamy are often outside a woman's control. As a result, there is a desperate need to develop methods which provide women-controlled prevention of HIV infection. We propose to develop a novel intravaginal delivery system which can locally induce mucosal immunity for extended periods of time. To date, there are currently no vaccines that can successfully protect an individual from HIV infection. In the case of HIV vaccines, it is ideal to elicit mucosal immunity at the site of transmission (ie. vagina). To our knowledge, there are currently no vaccines designed for local administration via the vagina and most importantly there are no studies examining the impact of sustained induction of mucosal immunity on the prevention of HIV type I infection (HIV-1). To accomplish this, we will develop a novel intravaginal ring formulation composed of medical-grade polyether urethane (PU). The inexpensive cost along with the ability to control the physical and chemical properties of the PU make it a suitable material for the delivery of proteins. We are interested in delivering the proteins gp120 (a component of the envelope glycoprotein of HIV-1) and IL-12 (cytokine used as an adjuvant) for inducing mucosal immunity. Studies have shown that administration of both gp120 and IL-12 can elicit the production of neutralizing antibodies against HIV-1. We hypothesize that by administering low, continuous doses of gp120 and IL-12 over extended periods of time (>30 days), the continuous elevated levels of mucosal antibodies will provide a more effective method of protecting against HIV-1 infection. If we are successful, this system could be a breakthrough platform for inducing mucosal immunity to a variety of sexually transmitted pathogens and could be a significant breakthrough in women's health.