- Moderna's mRNA tech could change the game in the decades-long effort to develop an HIV vaccine.
- The company said it expects to begin two vaccine trials in humans by the end of 2021.
- While "excited" by the prospect, HIV researchers caution there's a long road ahead for mRNA vaccines.
- See more stories on Insider's business page.
The company's mRNA technology, which has built upon decades of research, will now contribute to the long frustrated effort to contain the global HIV/AIDS epidemic.
Working in collaboration with the National Institutes of Health, Scripps Research, the Gates Foundation, and other partners, Moderna said it would begin testing two HIV vaccine candidates in humans by the end of 2021.
The COVID-19 vaccine developer's long-term goal is to show that its mRNA-based vaccine can produce broadly neutralizing antibodies, a type of immune response that researchers believe will be protective against circulating HIV strains around the world.
"Think about the people who die of HIV every year, the people who aren't alive because they don't have the amazing therapy available in this country," CEO Stephane Bancel told Insider in an interview Tuesday. In 2019, 700,000 people died of AIDS-related causes, the disease caused by HIV, and an estimated 1.7 million individuals contracted HIV.
However, two veteran HIV/AIDS researchers told Insider that while they're excited by the prospect of using mRNA technology to develop an HIV vaccine, there's a long road ahead for all players involved. Moderna's mRNA technology will indisputably speed up the "fine-tuning" of HIV vaccine development, but only continued testing will show if the end result is actually safe and effective.
Emory University virology professor Rafick-Pierre Sekaly, who has studied HIV for two decades, said it would be "crazy not to test" whether mRNA technology could bypass the expensive, slow process of generating these protein fragments in the lab.
"We had such a spectacular outcome with coronavirus that we absolutely need to embark on this platform and test it," Sekaly said. "None of the other [HIV] platforms have generated any inkling of promising results."
Moderna's partnership will build on a new and unproven vaccine approach
William Schief, an immunology professor at Scripps Research and vaccine design director of the International AIDS Vaccine Initiative, presented Moderna's investors with unpublished data from an HIV vaccine trial presented at a virtual AIDS research conference in February.
The trial, which started in 2018, was conducted with 48 HIV-negative adults, and will serve as preliminary basis off which Moderna and its collaborators will further study and test a vaccine approach targeting broadly neutralizing antibodies. Subjects were given either a low or high dose of the protein-based vaccine candidate, which was designed to activate certain "naive" B cells of the immune system.
When activated, the B cells produce proteins that eventually give rise to the hoped-for broadly neutralizing antibodies.
"The importance of priming these naive B cells is the key first step," Schief said on the investor call. "If you can't get that to work, the whole thing isn't going to work."
After being treated with the experimental vaccine, 47 out of 48 participants showed the targeted levels of naive B cells critical in eventually producing the antibodies, though the data remains subject to peer review. The final study volunteer dropped out.
Moderna's cost and time-efficient mRNA technology will speed up the process of conducting clinical trials, Schief said. Relatively speaking, conventional in-lab protein manufacturing is slow and expensive.
"It took us years just to do that one trial, many years," he added, referring to 48-person study. "We need to do a lot of human clinical trials, and we think that Moderna mRNA is the technology that will let us do that."
Moderna plans to test two mRNA-delivered HIV vaccine candidates in humans, both of which will test for safety and efficacy. The first is based on the initial study's protein component, while the other will determine whether synthetic HIV-like antigens can provoke the desired immune response. Both trials will start by the end of this year.
Compared to the virus behind COVID-19, HIV is a 'very different ballgame'
Dr. Ian Frank, an HIV vaccine researcher at the University of Pennsylvania who's helped develop HIV vaccines including one that made it to late-stage trials in 2007, said that the mRNA approach to developing an HIV vaccine has the advantage of speed and flexibility. Without scrutinizing the data from Schief's study, which is still undergoing peer review, it's a little difficult to understand the nuance, he said.
However, if the data show the vaccine created broadly neutralizing antibodies, this approach would signal a complete paradigm shift for HIV vaccine research, Frank said.
Despite the success of using mRNA to immunize against COVID-19, HIV is a "very different ballgame," Sekaly, the HIV researcher at Emory University, said. Once infected with HIV, the virus remains permanently active in a small number of cells in the body if left untreated, unlike the virus that causes COVID-19.
This means that a successful HIV vaccine has to overcome a higher hurdle than any other vaccine in history, Frank said. It would need to prevent infection, or the immune response underlying it, entirely. Other vaccines, including both Moderna and Pfizer-BioNTech's COVID-19 vaccines, only prevent the development of an infection into illness.
"For us to have an HIV vaccine that is effective in a way that will lead to prevention of infection, there's some fine tuning of this vaccine that is gonna need to happen," Frank said.
Although "excited" by the prospect of the Moderna partnership in HIV vaccine trials, Sekaly stressed that the mRNA-based delivery approach is still unproven beyond COVID-19, and emphasized the need for patient safety in clinical trials.
Both Frank and Sekaly said that the company's mRNA platform would likely enable any promising vaccine candidates to move from early to mid-stage clinical trials within a year - a much faster pace than vaccine development has historically gone.
Moderna's mRNA candidates have breakthrough potential in the frustrating, costly search for an HIV vaccine
Speaking to Insider, company CEO Bancel acknowledged the inherent challenge in developing a safe and effective HIV vaccine, a global health problem whose solution has eluded researchers for four decades.
The last HIV vaccine candidate that had made it to late-stage studies in South Africa stopped in February 2020 after there was "absolutely no evidence of efficacy," its head researcher told Science.
An earlier version of the vaccine used in the South African study had only shown 31% efficacy in a previous trial in Thailand. Before that, the last HIV vaccine to make it to a late-stage clinical trial concluded in 2007.
The two remaining late stage clinical HIV vaccines trials, Mosaico and Imbokodo, are being run by Johnson & Johnson and will not release results before the end of 2021.
Like the South African study halted in 2020, both trials use an inactive viral vector carrying genetic material based on HIV's many strains from around the world, as well as a synthetic protein mimicking part of a particle's envelope protein.
Even without Moderna involved, the HIV vaccine designed by Schief's team takes a different approach to tackling the virus than the one used in the J&J trials. By using the same delivery method as both Moderna's and Pfizer-BioNTech's COVID-19 vaccines, researchers will be able to fine-tune versions of their vaccine even further, Frank said.
COVID-19 vaccines have benefited from decades of HIV vaccine research
Although he finds the prospect of an mRNA vaccine exciting, Frank said Moderna and its partners have a long road ahead in proving if their mRNA-delivered protein approach is successful.
"The strategy has the potential to be a breakthrough, but it's the first step in a hard climb," Frank said. Moderna's mRNA technology will definitely give researchers the ability to test quickly, but that's all he can conclude.
"I'm sure they can get a candidate vaccine," Frank said. "The challenge will be how effective of an immune response it elicits."
The COVID-19 were been the breakthrough moment for mRNA vaccines, creating inroads for further HIV and cancer research. However, according to a recent National Bureau of Economic Research paper, it was actually decades of collective failure and the billions of dollars poured into HIV vaccine research that laid the foundation for the COVID-19 vaccines.
Published in March, author Jeffrey E. Harris found that 86% of clinical COVID-19 vaccines could trace their scientific basis to past HIV vaccine trials. From this vantage point, Moderna's mRNA platform is actually just a brief interlude from directly HIV-oriented scientific research driving the latest efforts in curbing the HIV/AIDS epidemic.
Andrew Dunn contributed reporting.