Characterization of the Host Antibody Responses Against anti-HIV/SIV Antibodies Delivered with AAV

Long-term delivery of neutralizing antibodies by means of recombinant adeno-associated virus (rAAV) is a novel and promising approach for the prevention or treatment of HIV infection since it circumvents the difficulties of generating a successful immunogen or vaccine. It is also cost-efficient: one single injection accounts for long-term expression (years) of the desired antibody or antibodies. However, host antibodies raised against the delivered protein are a serious concern that could compromise the efficacy of this approach by reducing the concentration and functionality of the delivered antibody. A better understanding of how anti-antibody responses arise is crucial to make this a reliable approach. In this webinar we will describe the dynamics and characteristics of the anti-antibody responses in macaques that received either a combination of anti-HIV antibodies (10-1074, 10E8 and 3BNC117 or 1NC9, 8ANC195 and 3BNC117) in therapy trials or anti-SIV antibodies in prevention trials. Overlapping peptide screening (Pepscans) demonstrated generation of anti-idiotypic antibodies. A correlation was found between the level of divergence of the delivered antibody from germline and the magnitude of the host response. Our results indicate that the problem of anti-anti responses will need to be overcome for the promise of this AAV antibody-delivery strategy to be effectively realized.

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