While antiviral medications limit the impact of the disease on daily life, human immunodeficiency virus (HIV) continues to infect 1.7 million people annually and cause some 770,000 deaths each year, which makes research on the virus a high priority.

Recently, a team that includes researchers from the Yerkes National Primate Research Center (YNPRC) at Emory University showed a new HIV vaccine is better at preventing infection and also lasts longer.

According to the researchers, the new vaccine’s improved protection lies in the combination of two types of immune responses: “neutralizing” antibodies and cellular immunity, a process involving the activation of T cells.

”Most efforts to develop an HIV vaccine focus on activating the immune system to make antibodies that can inactivate the virus, so-called neutralizing antibodies,” said Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory, and a researcher at the Emory Vaccine Center (EVC) and YNPRC. “We designed our vaccine to also generate a strong cellular immune response that homed in on mucosal tissues so the two arms of the immune response could collaborate to give better protection,” he continues.

In the study, the researchers inoculated three groups of 15 monkeys during a 40-week period.

The first group received Env, a protein on the virus’ outer surface known for stimulating antibody production, plus an adjuvant, a chemical combination often used in vaccines to enhance immune response.

The second group received the same, plus additional injections of three different attenuated (weakened) viruses modified to contain the gene for an HIV viral protein, Gag, which is known to stimulate cellular immunity.

A third, the control group, received injections containing only the adjuvant.

Following the 40-week regimen, all animals rested for 40 weeks, and then the researchers gave them booster shots of just the Env inoculation. After resting four more weeks, the researchers gave the animals 10 weekly exposures to SHIV, the simian version of HIV.

The results revealed animals in the two experimental groups experienced significant initial protection from viral infection if their immune system had a strong showing of neutralizing antibodies. Even more notable, say the researchers, was several of the Env-plus-Gag animals—but none of the Env animals—remained uninfected even though they lacked robust levels of neutralizing antibodies.

This outcome is exceptional because the potency of neutralizing antibodies has previously been thought to be crucial to a vaccine’s effectiveness. What’s more, when the researchers rechallenged the protected animals six months after the first challenges, the Env-plus-Gag animals but not the Env animals maintained protection, which shows the protection is durable.

“These results open exciting opportunities for HIV vaccines,” said Rama Amara, PhD, a Yerkes and EVC researcher and professor of microbiology and immunology at Emory. We now know it’s possible to achieve durable protection against HIV with a low response of neutralizing antibodies as long as the vaccine induces T cells.”

The team will use these results to refine the way it approaches vaccine development, noting a similar approach could possibly be feasible for other pathogens, including influenza, tuberculosis, malaria and COVID-19.

As the search for a cure continues, scientists across the NPRC network are working to discover new ways of treating and preventing HIV. Learn more about similar studies here.