What are Vaccines for HIV Prevention and Therapy?
Today there are no HIV vaccines which can prevent HIV infection. All of the candidates being studied are in the experimental stage. Preventive vaccine candidates are being tested in HIV-negative people. Some of these candidates are being tested to see if they can prevent infection. Other candidates are being tested to see if they lower viral load in people who receive the vaccine before becoming HIV infected but can learn to partially fight the resulting infection.
In 2013, investments in global preventive AIDS vaccine R&D declined by US$29 million, three percent, from US$847 million in 2012 to US$818 million in 2013. 2013 saw the largest real decrease in AIDS vaccine investment6 since 2008, following five years in which funding had either declined or flatlined from a height of $961 million in 2007. The substantial decrease in investment in 2013 was due primarily to the effects of mandated austerity measures taken by the US government, and in part to institutional and policy shifts within international development agencies in Europe and other countries.
The AIDS vaccine field grappled with difficult questions in 2013. In April 2013, HVTN 505, the only ongoing efficacy trial, halted immunizations of its DNA-adenovirus type 5 (Ad5) vaccine regimen because its Data Safety and Monitoring Board (DSMB) found that the vaccine did not prevent HIV infection, nor did it reduce viral load among vaccine recipients who became infected with HIV. The US-based trial, which was funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), was estimated to cost between US$75 and US$80 million and intended to run from 2009 to 2015. Researchers and funders met in September of 2013 to discuss the future for adenovirus platforms for AIDS vaccines, leading to the April 2014 publication by Dr. Anthony Fauci and colleagues at the NIAID of recommendations on moving forward with research on adenovirus-vectored vaccines. While no clinical trials using an Ad-5 based regimen are planned or enrolling, other adenovirus vectors-based vaccines have showed promise. Progress is being made with an Ad26-based vaccine set to begin a Phase I clinical trial in late-2014, to be funded by Janssen and NIAID.
The Pox-Protein Public-Private Partnership (P5) is funding and organizing a follow-up to the RV144 trial, where a pox-protein vaccine regimen was shown to reduce the risk of HIV infection by 31.2 percent after three years of follow-up, proving for the first time that a preventive AIDS vaccine is possible. Organizational and financial support for the P5 comes from NIAID, the Bill & Melinda Gates Foundation, the US Military HIV Research Program, Sanofi Pasteur, Novartis Vaccines and Diagnostics and the South African Medical Research Council (Box 4).
More than 30 other vaccine candidates were in the pipeline in 2013, most in early-stage trials. Basic research is ongoing to identify vaccine antigens that would stimulate immune systems to create broadly-neutralizing antibodies. Early- stage passive immunization trials supported by the NIH, and a vectored immunoprophylaxis trial led by the International AIDS Vaccine Initiative (IAVI), are underway, and could lead to testing of the concept that broadly-neutralizing antibodies can reduce the risk of HIV infection. Vaccine candidates using replicating vectors are also showing promising results, with IAVI’s Sendai virus vaccine currently in a phase I study in Kenya, Rwanda and the UK. China’s National Center for AIDS/STD Control and Prevention and China CDC are currently testing a replicating Tian Tan vaccine in a Phase II study.