Approaches to preventative and therapeutic HIV vaccines

•Non-efficacious preventative vaccines: gp120, Ad5 vector, DNA/Ad5.•Partially-efficacious preventative vaccine: ALVAC-HIV/AIDSVAX® B/E gp120.•Clade C ALVAC/gp120 constructs in phase 1 testing.•Antibody-mediated prevention and treatment: VRC01 monoclonal antibody in advanced clinical trial.•Therapeutic Tat vaccine: immune restoration, less immune activation, lower HIV-DNA.

Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Non-efficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials.