The fifth HIV vaccine concept in the history of the epidemic is currently being tested for efficacy in humans, and early findings appear to be encouraging.

It’s been more than 35 years since the emergence of the global HIV/AIDS epidemic, and over that time, the hunt for an HIV vaccine has proven to be a long-winding, elusive road for researchers.

However, new findings from an early-stage clinical trial of a potential HIV vaccine candidate have proven to be encouraging.

A new study published in The Lancet shows a positive immune response to an HIV-1 vaccine in adult humans and rhesus monkeys.

Beyond this, the vaccine candidate was shown to protect monkeys from simian-human immunodeficiency virus (SHIV), an HIV-like virus that only affects monkeys. While we haven’t yet seen the development of a definitive HIV vaccine, this research is having a ripple effect in the field.

A second-phase clinical trial in southern African countries is going on right now, testing 2,600 women who are at risk for contracting HIV.

Early results from the study, known as the APPROACH clinical trial, were initially presented at last year’s International AIDS Society Conference on HIV Science in Paris.

The team, led by researcher Dr. Dan H. Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, Massachusetts, gave the trial of the “mosaic” vaccine (which means that they took parts of different HIV viruses and combined them in one vaccine to try to elicit an immune response to a range of HIV strains) to 393 healthy adult participants from Rwanda, South Africa, Thailand, Uganda, and the United States.

“This study demonstrates that the mosaic HIV vaccine candidate induced robust and comparable immune responses in humans and monkeys. Moreover, the vaccine provided 67 percent protection against viral challenge in monkeys,” Barouch wrote in an email to Healthline.

He said that these results led to the second-phase southern African trial, with results expected to come out in 2021.

“This is only the fifth HIV vaccine concept that will be tested for efficacy in humans in the 35-plus-year history of the global HIV epidemic,” he noted.

Efforts to create an effective HIV vaccine have proven a big challenge over the years. The results of the first vaccine trial to show any positive protection against HIV were published in 2009 in the New England Journal of Medicine.

That study was carried out in Thailand, with 16,402 adult men and women given vaccine and placebo injections. It found that the men who received the vaccine had about a 31 percent lower infection rate than those who got the placebo. While it wasn’t high enough to qualify as a licensed vaccine, it paved the way for this most recent research.

“This new research is very encouraging and quite exciting. But we have to keep in mind that HIV is a virus with certain unique things that make it exceedingly resistant to the creation of a vaccine,” said Dr. Ronald G. Collman, director of the Penn Center for AIDS Research in Philadelphia, Pennsylvania.

Collman, who is not affiliated with Barouch’s research, tells Healthline that HIV is particularly “genetically heterogenous” compared to other viruses.

He says to create an effective vaccine, scientists would have to create antibodies that could recognize a wide range of potential strains of the virus. (Think of how a new flu vaccine has to be created every year. Collman points out there is even more variability in the HIV virus.)

Beyond this, Collman adds that HIV is coated in an “envelope protein” that is particularly “flexible,” making it able to wriggle away from antibodies that would effectively try to attack the virus. The HIV virus also rapidly develops reservoirs once it infects a cell.

“They permanently become a part of that cell forever, establishing these permanent reservoirs,” he explains.

Essentially, HIV is a tough virus to crack.

However, Collman says that after many unsuccessful attempts, the 2009 Thailand study opened the door for the kind of work being done now. He said that the new research certainly “is the kind of step you want to see before you roll out a large vaccine trial.” He cites the immune response in monkeys with SHIV as a positive step forward.

Of course, it isn’t a perfect correlation between that and human response to potential HIV vaccines, but he said it could give the researchers a solid reference point moving forward as they go on with the trial.

The hunt for an HIV vaccine has been something of a holy grail for scientists over the years. There certainly has been pressing need for a vaccine.

Since the start of the epidemic, more than 70 million people have been infected with HIV and about 35 million have died from it.

Sub-Saharan Africa is the region most impacted by the virus, with one out of every 25 adults living with HIV, according to the World Health Organization. In the United States alone, an estimated 1,122,900 adults and adolescents were living with HIV by the end of 2015, according to the Centers for Disease Control and Prevention.

Beyond the work of Barouch and his team, researchers from the National Institute of Allergy and Infectious Diseases (NIAID) recently published a study in Nature Medicine that looked at an experimental vaccine that targets a vulnerable area of HIV, producing antibodies in test animals like monkeys and mice.

The experimental vaccine neutralized a large portion of common strains of HIV. The researchers plan on launching a human trial of their vaccine in 2019.

Dr. Susan Buchbinder, a professor at the University of California, San Francisco, and the director of Bridge HIV, an HIV prevention research unit at the San Francisco Department of Public Health, tells Healthline that this research and the APPROACH study are examples of work being done globally by a wide network of researchers seeking to discover an HIV vaccine.

She says there is currently research being done in South Africa that is building off the promise of the older Thailand study.

“Really our hope is that we can further modify and get better and better vaccine products that can administer more robust immune responses and last for longer periods of time,” she said. “Ideally, we would be working in multiple populations and get strong results that could allow us to produce a product that would be maximally useful to the global population.”

Buchbinder is the co-chair of the “Imbokodo study,” the sub-Saharan Africa trial-phase of the APPROACH study that is taking place right now in South Africa, Zimbabwe, Mozambique, Malawi, and Zambia.

She says that Barouch’s study is an example of the best way to use animal testing to predict what could happen in humans. She said that since scientists would never expose a human to HIV, there is always more guesswork involved in human testing that doesn’t happen with an animal study.

The Imbokodo study is sponsored by Janssen Vaccines & Prevention, B.V. and was co-funded by NIAID as well as the Bill & Melinda Gates Foundation. NIAID Director, Dr. Anthony Fauci, tells Healthline that in the grand scheme of things, we’ve certainly made progress in the hunt for an HIV vaccine, but that more work needs to be done.

“The (Imbokodo) trial is part of gradual incremental progress that we are making,” Fauci said. “We are taking on one of the most important scientific challenges that we have ever had.”

He says we’ll have to wait and see if the trial works and then try to improve upon it down the line.

Looking to the future, Collman says he “doesn’t have a crystal ball” but is “encouraged that maybe it is possible” to develop an effective HIV vaccine down the line.

He said that, if anything, all of the work these researchers are doing could have a domino effect in infectious disease research for HIV and beyond.

“I think there is a reasonable chance we will have an HIV vaccine, but beyond that, what we’ve learned from work on the HIV vaccine will be incredibly valuable for other areas of progress,” he said. “All the tools and techniques and approaches that are being developed in the HIV vaccine field can be utilized, for example, in seeking a universal influenza vaccine. It could lead to other things like vaccines for herpes viruses and stuff like that. It’s like how they say ‘we wouldn’t have Teflon without the space program.’”

He added, “Even if we can’t develop an HIV vaccine right away, this work will be really valuable.”