Moderna to Begin Human Trials for Two Experimental HIV Vaccines

The vaccines are mRNA based, like the biotech company’s Covid-19 vaccine

An image of a T-cell infected with HIV taken with an electron microscope. The T-cell looks like a blue blob and it's against a red background. There are tiny yellow particles surrounding the blue structure. These are HIV virons.
The trials will test the safety of the two experimental vaccines and how well it stimulates a broad range of antibodies against HIV in the body. Pictured: An HIV infected T-cell. NIAID

The pharmaceutical and biotech company Moderna could begin human clinical trials for two new mRNA-based HIV vaccines as early as September 19, according to a study record posted to the United States National Institutes of Health Clinical Trial registry.

The vaccines will use a mechanism similar to the ground-breaking mRNA system in their Covid-19 vaccine, reports Science Alert’s Fiona Macdonald. The study is expected to take place until May 2023.

For several years, scientists have been researching the effectiveness and potential of mRNA vaccines for cancer treatments and other diseases in animal models. The Pfizer-BioNTech and Moderna Covid-19 vaccines were the first mRNA vaccines used in humans. The mRNA vaccines work by giving cells instructions to make bits of the same proteins on a virus’s outer shell. The proteins then prime immune cells to recognize and destroy the virus, reports Sarah Chodosh for Popular Science.

Researchers suspect multiple vaccines will be needed to generate an immune response strong enough to protect against HIV. HIV, or human immunodeficiency virus, is a retrovirus that attacks the body’s immune system. It’s difficult to prevent because it has a spike-like protein coated in a sugar-like residue that allows it to hide from antibodies when it enters the body, per Samuel Lovett for the Independent. Currently, there is no cure for HIV, only treatments that slow its progression.

Creating a vaccine that targets HIV is challenging because the retrovirus become part of the human genome 72 hours after transmission. To prevent infection, high levels of neutralizing antibodies must be present at the time of transmission, per Popular Science.

Scientists will assess the number of B cells in each study participant. B cells, also known as B lymphocytes, are a type of white blood cell that helps fight bacterial and viral infections. The vaccines are intended to prime B cells that have the potential to produce bnAbs, a type of highly potent neutralizing antibody, explains Karie Youngdahl, a spokesperson for the International AIDS Vaccine Initiative (IAVI).

Broadly neutralizing antibodies and their use in HIV research

Past research used a non-mRNA vaccine system, and 97 percent of participants did develop an immune response, Popular Science reports. Though the study was not designed to lead to a protective immune response yet, the research did successfully show a purified protein vaccine could stimulate rare B cells in a very specific way, Youngdahl says.

“We and others postulated many years ago that in order to induce bnAbs, you must start the process by triggering the right B cells — cells that have special properties giving them potential to develop into bnAb-secreting cells,” says William Schief, an immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, in a statement about previous reasearch. “In this trial, the targeted cells were only about one in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirms the ability of the vaccine immunogen to do this.”

Moderna’s new mRNA HIV vaccine system could help tackle this issue by priming "B cells that have the potential to produce bnAbs," Youngdahl explains. The neutralizing antibodies work by targeting the virus’s envelope—its outermost layer that protects its genetic material—to keep it from entering cells and infecting them. These antibodies can also target several HIV variants.

The trials will test the safety of the two experimental vaccines. Moderna’s mRNA HIV vaccines will be the first of this kind to reach human clinical trials, reports Science Alert. Fifty-six healthy participants between 18 and 56, who do not have HIV, will receive the vaccine, reports the Independent. Four groups will be part of the experimental trials, with two groups receiving a mix of the vaccines and the other two groups receiving only one of two vaccines. All groups will know which type of vaccine they are receiving.

“Moderna are testing a complicated concept which starts the immune response against HIV,” says Robin Shattock, an immunologist at Imperial College London, to the Independent. “It gets you to first base, but it’s not a home run. Essentially, we recognize that you need a series of vaccines to induce a response that gives you the breadth needed to neutralize HIV. The mRNA technology may be key to solving the HIV vaccine issue, but it’s going to be a multi-year process.”

Editor's Note, August 27, 2021: A previous version of this article incorrectly stated the relationship between B cells and bnAbs. The story has been edited to correct that fact. The story has also been updated with comments from IAVI.

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