When Will HIV Be Stopped With a Shot?

Since HIV was first identified decades ago, only five potential vaccines have been approved to test on humans. Thankfully, the summer of 2018 was brimming with news of promising advancements for contenders into human clinical trials in the race for a vaccine. Here are a few:

According to findings published in the journal Natural Medicine, one new experimental vaccine regimen is tailor-made to fit the structure of a vulnerable region of HIV. The results generated antibodies in mice, guinea pigs, and monkeys, while neutralizing dozens of HIV strains. The findings might lead to human clinical trials for a vaccine capable of neutralizing a large fraction of common HIV strains.

Led by investigators from the National Institute of Allergy and Infectious Diseases, which falls under the National Institutes of Health, a preliminary human trial of the team’s new vaccine regimen is anticipated to begin in the second half of 2019.

The study was spearheaded by Peter D. Kwong, Ph.D., chief of the Structural Biology Section at the NIAID Vaccine Research Center, and John R. Mascola, M.D., the center’s director.

“NIH scientists have used their detailed knowledge of the structure of HIV to find an unusual site of vulnerability on the virus and design a novel and potentially powerful vaccine,” stated NIAID director Dr. Anthony S. Fauci. “This elegant study is a potentially important step forward in the ongoing quest to develop a safe and effective HIV vaccine.”

The vaccine is epitope-based. An epitope is the specific site on an antigen where an antibody binds. It is based on the site of a broad number of HIV strains that antibodies can bind to. This epitope was just identified two years ago.

Investigators engineered many immunogens, or proteins, designed to activate an immune response to create the vaccine, using the known structure of the fusion peptide. The winning immunogen consisted of eight amino acids of the fusion peptide bonded to a carrier that generated a strong immune response. They also paired this immunogen with a replica of the HIV spike.

Investigators then tested different combinations of injections of the protein, plus an HIV spike in mice, and analyzed the antibodies that the vaccine regimens generated. The antibodies, as planned, attached to the HIV fusion peptide and neutralized up to 31 percent of viruses from a panel of 208 HIV strains from around the world.

For the next step, investigators moved onto guinea pigs and monkeys — which also generated antibodies. Once they are able to determine a version safe enough for human trials, they can move forward and carefully test it on volunteers.

Another leading contender called the Ad26/Env HIV-1 vaccine was announced to move into Phase 2b human clinical trials using adult volunteers in southern Africa. This exciting vaccine is being developed by a team of researchers at Harvard Medical School.

As a “mosaic” vaccine, it was developed to protect against a broad patchwork of HIV strains. Ad26/Env HIV-1 has already demonstrated immune responses in HIV-negative rhesus monkeys, protecting them from contracting the virus in 67 percent of exposures. (While successful, that isn’t effective enough alone to garner FDA approval.)

The investigation was led by Dan H. Barouch, M.D., Ph.D., director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in collaboration with Janssen Vaccines & Prevention and other organizations.

In findings published in The Lancet, the Phase 1/2a trials, also known as APPROACH, tested five regimen versions of the vaccine on 393 HIV-negative adult volunteers in Rwanda, South Africa, Thailand, Uganda, and the United States. According to researchers, all five regimens proved to produce a robust immune response. So far, scientists have been “cautiously optimistic” about the results. Barouch’s team expects results on human trials on Ad26/Env HIV-1 to be made available by 2021 or 2022.

There are more HIV vaccines in development, in various stages of clinical trials. Other broadly neutralizing HIV vaccine candidates are currently being observed in HVTN 702 and Imbokodo clinical trials. The Imbokodo trials, for instance, are examining the efficacy of combining two vaccines: Ad26.Mos4.HIV (Ad26 vaccine) and Clade C gp140 (a protein vaccine). Imbokodo trials have also entered into Phase 2b with human participants.

Now, investigators are looking to improve vaccine effectiveness by making them more potent, possibly by combining multiple vaccines (sometimes in a series of shots) to produce more consistent results and, ultimately, a broadly neutralizing vaccine fit for the public and capable of preventing most strains of HIV.