Effect of pre-existing adenovirus neutralizing antibody on vector infectivity and transgene expression

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Description: Adenoviruses were identified as unique viruses in 1953 by Rowe and coworkers when virus was isolated from human adenoids. Because adenoviruses infect various cells they are considered an excellent vector delivery system. A major obstacle to efficient infection by recombinant adenoviruses is the humoral immune response, producing neutralizing and non-neutralizing antibodies in response to natural and recombinant adenoviruses. Neutralizing antibodies block the spread of virus and reinfection, suppressing viral gene expression and accordingly, gene therapeutics. Most humans have preexisting neutralizing antibodies to common adenoviruses. Unique approaches are needed to evade the effects of preexisting neutralizing antibodies. My hypothesis was that propagation of adenovirus vectors in the presence of serotype-specific neutralizing antibodies would result in selection of hexon mutants resistant to immune inactivation. I found one Adenovirus6 (Ad6) sequence, NPD-06 contained 7 differences from the GenBank reference Ad6 sequence. These resulting mutations may be sufficient to evade immune inactivation.
Language: English
Format: Degree Work