Florian Hladik from the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, USA, explains why recent research on how to study the rectal and genital mucosa – featured in the new PLOS Collection Advances in HIV Mucosal Immunology: Challenges and Opportunities – will be key to developing an effective HIV vaccine.
People most often become infected with HIV through sexual transmission; accordingly, their initial exposure to the virus is in their genital or rectal mucosa. Consequently, the best opportunity to prevent HIV transmission is through interventions that affect the mucosa. For example, new HIV infections could be prevented by reducing the amount of virus in the genital fluids of infected people or by stopping HIV from establishing productive infections in the genital or rectal mucosa of uninfected people. In order to design HIV interventions that work this way, we must first understand how best to study the mucosa so that we can determine whether test interventions are effective.
So far, the best HIV prevention strategies have involved drug treatment. Antiretroviral (ARV) treatment of people who are infected with HIV decreases their viral load (the amount of active virus in their blood and genital fluids), so they are less likely to pass on the virus. Similarly, when uninfected people take ARV drugs prophylactically, their risk of infection decreases if they are exposed to HIV. In 2012, the U.S. Food and Drug Administration approved an oral pill, Truvada, for uninfected people to use for this purpose. The effectiveness of this kind of pre-exposure prophylaxis (PrEP) depends on adherence to daily dosing.
Despite these successes, a vaccine remains the Holy Grail of HIV prevention. When HIV was first identified in 1982, scientists thought we’d have an effective vaccine within a few years. But more than 30 years later we look back in awe at how HIV has repeatedly out-manoeuvred us. Among the many challenges to the development of an effective HIV vaccine has been the technical difficulty of assessing a vaccine’s impact on the mucosal immune system. Without reliable methods to evaluate how the mucosal immune system responds to an experimental HIV vaccine, we are missing important information about how well that vaccine worked—and how to improve the next one.
In 2009, the U.S. National Institute of Allergy and Infectious Diseases provided seed funding to the HIV Vaccine Trials Network (HVTN) to address these challenges by establishing the HIV Mucosal Immunology Group (MIG). Since 2013, the Bill & Melinda Gates Foundation has provided additional funding for this endeavor. The MIG comprises a group of expert scientists who are coordinating their efforts to improve mucosal sampling, specimen storage and assay technologies, with emphasis on methods that gain maximum information from limited amounts of mucosal secretions, cells and tissues. In the newly launched PLOS Collection Advances in Mucosal Immunology: Challenges and Opportunities MIG investigators report the results of their efforts, providing important, practical details on studying immune responses in the genital and rectal mucosa, which will help guide future studies of HIV prevention with vaccines and topical microbicides.
Concurrently, another MIG-initiated resource, co-developed by NIAID and the Global HIV Vaccine Enterprise, has been published by the Global HIV Vaccine Enterprise: Capturing Participant Information for Mucosal Sampling: An Investigator’s Guide. Lessons learned from MIG research efforts to standardize and optimize methods for mucosal sample collection, processing and analysis will also be featured in a public, NIAID workshop “Best Practices in Mucosal Sampling” held on May 1st at the NIH campus.
Florian Hladik obtained his MD PhD and Dermatology/Venereology training at the University of Vienna in Austria. He carried out postdoctoral research at the Johannes Gutenberg University in Mainz, Germany, and the University of Washington, USA. He is currently Research Associate Professor in the Departments of Obstetrics and Gynecology and Medicine, University of Washington, and Affiliate Investigator at the Fred Hutchinson Cancer Research Center in Seattle, USA. His research focuses on HIV transmission pathogenesis and the impact of HIV prevention strategies on the mucosa. He has no conflicts of interest.