Clark, N. M.; Keles, N. K.; Hagedorn, G. N.; Klenchin, V. A.; Andersen, H.; Treece, J.; Fennessey, C. M.; Xie, J.; Denny, T. N.; DeMarco, C. T.; Hernandez, J. S.; Capuano, S.; Gardner, M. R.; Keele, B. F.; Gao, G.; Lewis, M. G.; Roederer, M.; Evans, D. T.

Conventional vaccines have so far failed to elicit the types of antibodies needed for protection against HIV. As an alternative, we evaluated adeno-associated virus (AAV) delivery of rhesus macaque antibodies to the SIV envelope glycoprotein for protection against SIV challenge. AAV vectors encoding a broadly neutralizing antibody (bnAb) and an antibody that only mediates antibody-dependent cellular cytotoxicity (ADCC) were administered individually or together to separate groups of rhesus macaques. Antibody expression was sustained for more than a year with minimal anti-drug antibody responses. All animals that received a control antibody or the ADCC-only antibody became infected after five low-dose, intrarectal challenges with SIVmac239. In contrast, 14 of 16 animals that received the bnAb resisted two rounds of twelve SIVmac239 challenges more than a year apart. Thus, AAV delivery of a single bnAb can afford durable protection against a pathogenic SIV strain that is notoriously difficult to protect against by vaccination.