Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial

Publication date: Available online 15 March 2019Source: The Lancet HIVAuthor(s): Frances H Priddy, David J M Lewis, Huub C Gelderblom, Hana Hassanin, Claire Streatfield, Celia LaBranche, Jonathan Hare, Josephine H Cox, Len Dally, Daryl Bendel, David Montefiori, Eddy Sayeed, Jim Ackland, Jill Gilmour, Bruce C Schnepp, J Fraser Wright, Philip JohnsonSummaryBackgroundA preventive vaccine for HIV is a crucial public health need; adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunisation to induce sustained expression of neutralising antibodies to prevent HIV. We assessed safety and tolerability of rAAV1-PG9DP, a recombinant AAV1 vector encoding the gene for PG9, a broadly neutralising antibody against HIV.MethodsThis first-in-human, proof-of-concept, double-blind, phase 1, randomised, placebo-controlled, dose-escalation trial was done at one clinical research centre in the UK. Healthy men aged 18–45 years without HIV infection were randomly assigned 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). Volunteers were followed up for 48 weeks. The primary objective was to assess safety and tolerability. A secondary objective was to assess PG9 expression in serum and related HIV neutralisation activi...
Source: The Lancet HIV - Category: Infectious Diseases Source Type: research