Postexposure Prophylaxis Against HIV 1 by Cd4 Igg2

An individual who is exposed to HIV-1 contaminated blood or other bodily fluids runs a significantbecoming infected with the virus. The goal of post-exposure prophylaxis is to protect exposed indivianticipated infection. The major clinical settings for HIV-1 post- exposure prophylactic therapy inctransmission as a result of accidental needle-stick injuries sustained by health care workers and veinfected pregnant woman to her newborn child. In this regard, passive transfer of human immunoglobulindividual has been successfully used to prevent or treat many viral infections of humans. In this Pdevelop a recombinant CD4-immunoglobulin protein, termed CD4-IgG2, as a novel post-exposure prophylaagainst HIV-1. CD4-IgG2 is a heterotetramer containing two chains of a CD4-human IgG2 heavy chain futwo chains of a CD4-human kappa light chain fusion protein. The major advantage of CD4-IgG2 is thatmolecules can neutralize all strains of HIV-1, including primary isolates of the virus. We will perfto determine the ability of CD4-IgG2 to neutralize a large panel of primary isolates of HIV-1, includifferent tropisms as well as strains isolated from different stages of the disease and from differevivo neutralization experiments will also be performed using viremic plasma from HIV-1-infected indiCD4- IgG2, several neutralizing monoclonal antibodies against HIV-1 will be included in these expericomparative analysis of the different agents. Finally, we will perform initial HIV-1 protection expemice (mice with severe combined immunodeficiency transplanted with normal human peripheral blood leuthe in vivo antiviral activity of CD4-IgG2. The hu-PBL-SCID mouse is a suitable model for evaluationfor prophylaxis HIV-1. The development of a safe and effective post-exposure prophylactic agent agaiurgent public health priority. The overall goal of this Phase I project is to determine the suitabildevelopment as an immunoprophylactic agent.