Over the past year, there has been a dramatic shift in the amount of space vaccines occupy in the public consciousness. During the development and testing of the current Covid-19 vaccines, people followed the different phases of the clinical trials like an early season of American Idol. In fact, many referred to and thought of it as the “race for a vaccine.” This, of course, makes sense, given that from the very start of the pandemic, public health officials made it clear that having a safe, effective vaccine was our ticket back to some type of normalcy.
Several months into the rollout, vaccines are still very much on our radar. While that truly is a win for public health, last week there was widespread confusion over clinical trial findings first made public in February. According to several dramatic headlines and exuberant, widely shared social media posts, thanks to technology developed by Moderna for their Covid-19 vaccine, a highly effective HIV vaccine is well within reach — like a modern-day public health fairytale.
Unfortunately, that didn’t happen. But some combination of misinterpreting the study’s findings, and our ongoing thirst for vaccine news, resulted in that feel-good narrative going viral. (Sorry.)
Meanwhile, the actual results of that study do genuinely represent a significant breakthrough, bringing researchers one step closer to the development of vaccines not only for HIV, but other viral infections as well. Here’s what to know about these legitimately exciting findings.
Confusion and vaccine enthusiasm aside, why are we talking about this research?
The short version is that this was the first clinical trial conducted on humans to successfully utilize an approach that primes the immune system to develop a specific type of antibody — a key component of a future HIV vaccine.
Specifically, they found that 97 percent of the participants who received the vaccine had the immune response researchers were hoping for. (And yes, this approach was tested via two doses of a vaccine, which may have added to some of the confusion about the findings.)
Known as IAVI G001, the clinical trial was a proof of concept study — meaning that its aim was to determine if this particular method shows enough promise to warrant further research. (It did.) The study was a collaboration between the International AIDS Vaccine Initiative (IAVI) — which was also the official sponsor of the trial — and Scripps Research, and funded via grants from the Bill & Melinda Gates Foundation and National Institute of Allergy and Infectious Diseases (NIAID), among others.
How does this vaccine approach work?
Before getting into specifics of this particular clinical trial, it’s important to have some context, says Dr. Mark Feinberg, the president and CEO of IAVI. Though he wasn’t part of the research team that conducted this clinical trial, Feinberg has more than 20 years of experience researching HIV/AIDS, and the biology of other emerging diseases.
“It is easier for the immune system to mount a potent effectively neutralizing antibody response to SARS-CoV-2 [than HIV],” he tells Rolling Stone. “It is incredibly difficult to do with HIV, and that’s just due to fundamental differences in the viruses and the kinds of infections that they cause.”
This helps explain — at least from a scientific perspective — why researchers were able to develop multiple effective Covid-19 vaccines in less than a year, while research into an HIV vaccine has been going for decades. To date, no HIV vaccine study has been able to induce broadly neutralizing antibodies by vaccination — something Feinberg and his colleagues believe is an integral part to developing an effective HIV vaccine. Broadly neutralizing antibodies (bnAbs) are rare but powerful specialized blood proteins that can counteract many different strains of a virus — something especially important with HIV, which mutates far more frequently than other viruses.
“We’re worried about Covid [variants], but what Covid does in two months, HIV does in one day,” says Dr. Larry Corey, a virologist at Fred Hutchinson Cancer Research Center and co-founder of the HIV Vaccine Trials Network (HVTN). In addition to his contributions to HIV research — including the development of antiretroviral medications — Corey was one of two scientists Dr. Anthony Fauci tapped to oversee the more than 80 clinical trial sites developing Covid-19 vaccine candidates during Operation Warp Speed.
As someone familiar with both viruses but not involved with IAVI G001, Corey explains that while developing an effective HIV vaccine is “a much more formidable challenge” than creating one for Covid-19, “this breakthrough was a good one.”
What exactly was that breakthrough?
The vaccine tested in the IAVI G001 clinical trial was specifically designed to activate certain cells that have the potential to produce bnAbs. “We have to walk the immune system down this path to make broadly neutralizing antibodies,” Feinberg explains, noting that in 97 percent of the participants who received the vaccine, this approach “worked pretty much exactly the way we wanted it to work.”
Now, Feinberg says that researchers can shift their efforts towards achieving the next steps necessary to create an HIV vaccine.
Plus, researchers believe that this method of priming the immune system to produce bnAbs may also be applied to creating vaccines for other challenging pathogens like malaria, and the Zika and hepatitis C viruses. Similarly, Feinberg says that this approach also has the potential to play a role in developing a universal influenza vaccine — as in, one that will work on most strains, making our annual flu shot significantly more effective.
How does Moderna and the Covid-19 vaccine fit into the picture?
The reports that this HIV vaccine breakthrough was only possible thanks to the mRNA technology Moderna invented when developing their Covid-19 vaccine is inaccurate for several reasons. First, the research into whether RNA-based vaccines could work for HIV began long before anyone had heard of SARS-CoV-2. “HIV [vaccine research] created the backbone and the wherewithal that allowed us to do such an incredibly terrific lift on Covid,” Corey explains. Additionally, while Moderna has partnered with the research team to develop and test an mRNA-based vaccine that uses this approach to produce bnAbs, that is for the next step in the process — in other words, research that hasn’t happened yet.
Having said that, moving forward into the next phases of the research into an effective HIV vaccine, the lessons learned and techniques perfected during the development of a Covid-19 vaccine will certainly be an asset. “Hope springs that Covid teaching us how we do things will help us in HIV vaccines,” Corey says.
For one, utilizing RNA technology — which uses a messenger (mRNA) that acts as a piece of genetic code, prompting the body to make a decoy protein that resembles the virus, in the hopes that the immune system will be tricked into attacking it, ultimately ending in the development of antibodies to fight off the virus — is expected to speed up the pace of discovery and development efforts towards an HIV vaccine. “RNA technology is not going to, in and of itself, overcome the fundamental challenges to making an HIV vaccine — those are going to be the same,” Feinberg explains. “It’s just the tool that’s provided by the RNA technology that will allow us to move much more quickly and take our best ideas into human studies faster than we would have been able to do previously.”
How much faster are we talking? According to Feinberg, it’s still too early to have any type of timeline for the development of an effective HIV vaccine, but he does note that unlike the Covid-19 vaccines, this process will take more than a year.
What else could this mean for HIV vaccine research?
While some of the recent reporting on this clinical trial included what Feinberg refers to as “irrational exuberance around interpreting some of the data,” it’s promising to see that a year into our careers as armchair virologists, we’re still really excited about vaccines. “I think that there’s optimism here,” Corey says. “First of all, understanding about vaccines has markedly increased in the country, so the interest in developing vaccines is there.”
Throughout the pandemic, Corey says that he’s been worried that — like so many other things — HIV vaccine research would be “buried under Covid.” But now he’s hopeful that moving forward, the increased public awareness of vaccines and their development, thanks to Covid, will ultimately be a boon for HIV vaccine research.
“As we emerge from the Covid epidemic, I hope that there will be momentum,” he says. “And that the citizenry will participate in HIV vaccines like they did in Covid. I mean, how they helped us in Covid is miraculous — all these people stepped up, rolled up their sleeves, and got the critical shots.”
Editor’s note: This story has been updated to clarify that no HIV vaccine has yet been able to produce bnAbs.