Adeno-associated virus (AAV) is small safe viral vector that has been previously used to deliver antibodies in vivo (Fang et al. 2005). In the context of passive HIV immunization, Johnson and colleagues used AAV as a viral vector for delivery of antibody-like proteins that protected macaques from SIV infection (Johnson et al. 2009). More recent work has also demonstrated that AAV vectors expressing a HIV neutralizing antibody is able to protect humanized mice from HIV-1 infection (Balazs et al. 2012). This research will further assess AAV-delivery of additional broadly neutralizing antibodies. Administration of AAV vectors expressing HIV neutralizing antibodies are being tested to demonstrate their potential for sustained expression and their ability to confer long-lived protection against HIV infection and progression of disease.A major goal is to develop AAV vectors expressing multiple antibodies to increase the breadth of passive immunization therapy to cover strains resistant to any one neutralizing antibody. AAV is also being used in studies to test for protection against influenza. Influenza causes annual epidemics that lead to an average of over 20,000 deaths each year in the United States. Neither immunity created by prior infections nor current vaccines provide lasting protection against these epidemic because influenza virus undergoes rapid changes. The goal of this research is to evaluate the ability of an alternative approach, vectored-immunoprophylaxis, to direct the expression of broadly neutralizing antibodies against influenza and investigate whether such approach protects against infection.

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Georgiev, Ivelin S; Rudicell, Rebecca S; Saunders, Kevin O et al. (2014) Antibodies VRC01 and 10E8 neutralize HIV-1 with high breadth and potency even with Ig-framework regions substantially reverted to germline. J Immunol 192:1100-1106