A new HIV vaccine could be one of Moderna’s next MRNA success story

• Moderna’s mRNA technology could change the game during the decades-long effort to develop an HIV vaccine.
• The company said it expects to start two vaccination trials in humans by the end of 2021.
• While the prospect is ‘excited’, HIV researchers warn that there is a long way to go for mRNA vaccines.
• See more stories on Insider’s business page.

Moderna’s investor presentation on Wednesday showcased biotech-based efforts to develop vaccines against HIV and eight other infectious diseases.

The company’s mRNA technology, which has built on decades of research, will now contribute to the long-frustrated effort to curb the global HIV / Aids epidemic.

In collaboration with the National Institutes of Health, Scripps Research, the Gates Foundation and other partners, Moderna said it will begin testing two candidates against HIV vaccine in humans by 2021.

The COVID-19 vaccine developer’s long-term goal is to demonstrate that the mRNA-based vaccine can neutralize antibodies in general, a type of immune response that researchers say protects against HIV strains around the world.

“Think of the people who die annually from HIV, the people who do not live because they do not have the wonderful therapy available in this country,” CEO Stephane Bancel said in an interview with Insider on Tuesday. In 2019, 700,000 people died from AIDS-related causes, the disease caused by HIV, and an estimated 1.7 million individuals contracted HIV.

However, two veteran researchers on HIV / Aids told Insider that although they are excited about the prospect of using mRNA technology to develop an HIV vaccine, all those involved have a long way to go. Moderna’s mRNA technology will undoubtedly accelerate the “fine-tuning” of HIV vaccine development, but only ongoing testing will show whether the end result is actually safe and effective.

Rafick-Pierre Sekaly, professor of virology at Emory University, who has been studying HIV for two decades, said it would be ‘crazy not to test’ whether mRNA technology is the expensive, slow process of generating these protein fragments. in the laboratory can bypass.

“We had such a spectacular outcome with coronavirus that we absolutely must start on this platform and test it,” Sekaly said. ‘None of the others [HIV] platforms yielded any promising results. ‘

Read more: Modern bets that its mRNA technology will lead to a new wave of vaccines for diseases such as HIV. Here are the top 5 it works with beyond COVID-19.

Moderna’s partnership will build on a new and unproven vaccine approach

William Schief, an immunology professor at Scripps Research and director of vaccine design at 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 began in 2018, was conducted with 48 HIV-negative adults and will serve as a preliminary basis on which Moderna and its collaborators will further study and test a vaccine approach that neutralizes antibodies in general. Subjects received a low or high dose of the protein-based vaccine candidate, which is 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 antibodies that broadly neutralize.

“The importance of preparing these naive B cells is the first important step,” Schief said. “If you can not make it work, the whole thing is not going to work.”

After being treated with the experimental vaccine, 47 of the 48 participants showed the targeted levels of naïve B cells that are critical to eventually producing the antibodies, although the data remain subject to peer review. The final study volunteer moved in.

Schief says Moderna’s costly and time-efficient mRNA technology will speed up the process of clinical trials. Relatively speaking, the production of proteins in the laboratory is slow and expensive.

“It took us years to do just one trial, many years,” he added, referring to a 48-person study. “We have to do a lot of clinical trials on humans, and we think that Modern mRNA is the technology that allows us to 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 protein component of the initial study, while the other will determine whether synthetic HIV-like antigens can elicit the desired immune response. Both trials will begin by the end of this year.

Steven Ferdman / Getty Images

Compared to the virus behind COVID-19, HIV is a ‘very different ball game’

Dr. Ian Frank, a researcher on HIV vaccines at the University of Pennsylvania who helped develop HIV vaccines, including one who came to late trials in 2007, said the mRNA approach to developing An HIV vaccine has the advantage of speed and flexibility. Without examining the data from Schief’s study, which is still being peer-reviewed, it is a little difficult to understand the nuance, he said.

However, if the data show that the vaccine broadly neutralizes antibodies, this approach would be 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 ball game’, said Sekaly, the HIV researcher at Emory University. Once infected with HIV, the virus remains permanently active in a small number of cells in the body when left untreated, unlike the virus that causes COVID-19.

That means a successful HIV vaccine must overcome a higher hurdle than any other vaccine in history, Frank said. It should completely prevent infection, or the immune response beneath it. Other vaccines, including the COVID-19 vaccines from Moderna and Pfizer-BioNTech, only prevent the development of an infection to disease.

“For us to have an HIV vaccine that is effective in a way that will lead to the prevention of infection, there is a fine-tuning of this vaccine that needs to happen,” Frank said.

Although Sekaly was “excited” about the prospect of the Moderna partnership in HIV vaccine trials, he stressed that the mRNA-based delivery approach has still not been proven beyond COVID-19, and stresses the need for patient safety in clinical trials.

Both Frank and Sekaly said the company’s mRNA platform is likely to move all promising vaccine candidates from early to mid-stage clinical trials within a year – a much faster pace than the vaccine’s development has gone in the past. .

Moderna’s mRNA candidates have a breakthrough potential in the frustrating, expensive search for an HIV vaccine

In an interview with Insider, Bancel, the company’s CEO, acknowledges the inherent challenge of developing a safe and effective HIV vaccine, a global health problem that researchers have been avoiding for four decades.

The last researcher told Science that the last candidate for HIV vaccine that reached the late stage in South Africa stopped in February 2020.

In a previous version of the vaccine used in the South African study, only 31% were shown in a previous trial in Thailand. Previously, the last HIV vaccine taken at a late stage clinical trial was completed in 2007.

The two remaining late-stage clinical HIV vaccine trials, Mosaico and Imbokodo, are managed by Johnson & Johnson and will not announce results before the end of 2021.

As the South African study was discontinued in 2020, both trials used an inactive viral vector containing genetic material based on the many strains of HIV from around the world, as well as a synthetic protein that is part of the envelope protein. mimics.

Even without Moderna being involved, the HIV vaccine designed by Schief’s team follows a different approach to tackling the virus than that used in the J&J trials. Using the same delivery method as both Moderna and Pfizer-BioNTech’s COVID-19 vaccines, researchers will be able to configure the version of their vaccine even further, Frank said.

AP Photo / Oded Balilty, file

COVID-19 vaccines have benefited from decades of research into HIV vaccine

Although he finds the prospect of an mRNA vaccine exciting, Frank said Moderna and his partners have a long way to go to prove whether their mRNA-delivered protein approach is successful.

“The strategy may be the breakthrough, but it’s the first step in a hard climb,” Frank said. Moderna’s mRNA technology will certainly give researchers the ability to test quickly, but that’s all he can deduce.

“I’m sure they can get a candidate vaccine,” Frank said. “The challenge will be how effective it is to have an immune response.”

The COVID-19 was the breakthrough moment for mRNA vaccines, which created a pathway for further HIV and cancer research. However, according to a recent report by the National Bureau of Economic Research, it was decades of collective failure that spilled billions of dollars into HIV vaccine research that laid the foundation for the COVID-19 vaccines.

Author Jeffrey E. Harris, published in March, found that 86% of clinical COVID-19 vaccines could trace their scientific basis to earlier HIV vaccine trials. From this point of view, Moderna’s mRNA platform is only a short interval of direct HIV-oriented scientific research that curbs the latest efforts to curb the HIV / Aids epidemic.

Andrew Dunn reported.