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Conference
"An Ounce of Prevention: Innate and Adaptive Mucosal Immunity in Defense Against Sexually Transmitted Viral Infections" Dr. Ken Rosenthal (biography) English - 2002-04-15 - 44 minutes
Summary : The innate immune system is the first line of defense against invading pathogens and is particularly important in protection against infections at mucosal surfaces. Although long ignored and believed to be nonspecific, recent studies indicate that the innate immune system is capable of rapidly recognizing and responding to pathogens or 'danger' signals and plays a decisive and instructive role in shaping the adaptive immune response. Despite nearly two decades of research directed at inducing adaptive immune responses to HIV, no successful immunologic therapy or vaccine has been developed. Therefore, it may be important to develop novel approaches to elicit innate immunity. Since HIV-1 is primarily a sexually transmitted infection, vaccines capable of protecting against this virus must be capable of inducing long-term effective mucosal immune responses, especially in the genital tract. However, it still remains unclear how to best achieve mucosal protection and what mechanisms contribute to this protection. For a number of years we have been developing mucosal vaccines capable of inducing specific adaptive immune responses in the genital tract and protection against intravaginal (IVAG) virus challenge. This work initially focused on induction of mucosal immune responses and protection against IVAG infection with herpes simplex virus type 2 (HSV-2). We recently extended this work to show that intranasal immunization with inactivated gp120-depleted HIV-1 immunogen plus the mucosal adjuvant CpG oligodeoxynucleotides (ODN) induced potent immune responses in the genital tract and protection against IVAG challenge. Since CpG ODN has been shown to activate potent innate immune responses against infectious agents and trigger Th1-like immune activation, we investigated whether transmucosal delivery of CpG ODN to genital mucosa could protect or treat intravaginal infection with HSV-2. Our results show that local delivery of CpG ODN to the genital tract is very effective at preventing genital viral infection and clearly indicatesthat CpG-induced innate mucosal immunity is involved.
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