During the month of May, IMPACT will be highlighting USAID’s work in Global Health.

Few things really worth having are easily obtained. This old saw, though well worn, applies perfectly to vaccines. And it bears repeating as we approach HIV Vaccine Awareness Day—especially in light of the recent termination of HVTN 505, a clinical trial testing whether a candidate vaccine regimen could prevent HIV infection or slow progression to AIDS. The trial was halted when it became clear the regimen would fall short on both goals.

This is disappointing news; yet history has taught us that such setbacks are par for the course in vaccine development. Indeed, most of the vaccines now lauded as lifesavers—not least of which is the storied polio vaccine—came to us only after several decades of research peppered with setbacks. This is the nature of the effort: vaccine researchers learn through informed trial and error what works, and what does not, and use that knowledge to hone their strategies.

An HIV-positive child at the Muranga District Hospital in Kenya waiting for treatment. Photo credit: Casey Kelbaugh, Int’l Center for AIDS Care and Treatment Programs, Columbia Univ. School of Public Health

Most importantly, we must emphasize that the termination of HVTN 505 occurs against a backdrop of remarkable progress in HIV vaccine development. Another large trial, completed in Thailand four years ago, demonstrated that HIV can be prevented by vaccination. Although the protection was modest, researchers are now working to improve on those results. Further, some 30 early-stage HIV vaccine trials are currently being conducted around the world—and many researchers are advancing novel vaccine candidates.

With the support of donors, especially USAID and the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), IAVI and its partners are contributing to these efforts on several fronts, focusing primarily on vaccines against HIV subtypes that circulate in developing countries and emphasizing novel vaccine strategies.

A trial we recently initiated in Kigali, Rwanda, for example, tests a vaccine candidate that has been engineered to persist in the body, which we expect will boost the potency, durability and breadth of immune responses that can destroy HIV-infected cells. The candidate is devised to elicit those responses in the mucosal tissues that line inner body cavities, such as the gut, where sexually transmitted HIV establishes a beachhead in the early stages of infection. The trial will also be conducted with IAVI’s partners in London and Nairobi. With support from USAID and PEPFAR, through IAVI, the Kenya AIDS Vaccine Initiative (KAVI) in Nairobi has built the capacity to systematically evaluate immune responses in mucosal tissues. This capability will contribute to KAVI’s growing prominence as a center of excellence in clinical research.

Over the past couple of years, IAVI and other organizations have also made significant progress toward the design of vaccines to elicit broadly neutralizing antibodies against HIV. Such antibodies would stop HIV from infecting its target cells in the first place. Researchers at and affiliated with IAVI have analyzed the structure of such antibodies, charted their evolution in the body and, most recently, shown that it might be possible to kick-start their production with a tailored vaccine.

We suspect that both cell-killing and blocking antibody responses will be needed to prevent HIV infection by vaccination. Though we will probably face some setbacks advancing such strategies, researchers are making brisk progress toward that goal. All the evidence today suggests that, if we persevere, it is just a matter of time before HIV vaccines become available. That should serve as a source of inspiration to all of us on this HIV Vaccine Awareness Day.

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