Priddy FH, et al. - Considering that adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunization to induce sustained expression of neutralising antibodies to prevent HIV, researchers examined if rAAV1-PG9DP, a recombinant AAV1 vector encoding the gene for PG9, a broadly neutralising antibody against HIV, is safe and tolerable. In this first-in-human, proof-of-concept, double-blind, phase 1, randomized, placebo-controlled, dose-escalation trial, they performed random assignment of healthy men aged 18–45 years without HIV infection to receive intramuscular injection with rAAV1-PG9DP or placebo in the deltoid or quadriceps in one of four dose-escalating cohorts (group A, 4 × 10¹² vector genomes; group B, 4 × 10¹³ vector genomes; group C, 8 × 10¹³ vector genomes; and group D, 1·2 × 10¹⁴ vector genomes). Outcomes suggest that to prevent HIV, vectored immunoprophylaxis appears as safe in the small number of healthy volunteers. Serum neutralization in four volunteers was induced, intermittently for at least a year. The antibody expression was that much low that it could not be directly detected in the circulation. AAV vectors was used for the first time in healthy populations for antibody gene delivery for an infectious disease prevention indication. The participants well-tolerated rAAV1-PG9DP.