- Moderna has administered the first doses of its mRNA-based HIV vaccine to volunteers in a clinical trial.
- The vaccine delivers instructions to HIV-specific antigens that could potentially induce certain immune responses.
- The development of an HIV vaccine has taken decades, and the mRNA technology may help speed up the process.
The first doses of an experimental HIV vaccine that uses Moderna’s mRNA technology have been given to participants in a phase 1 clinical trial, the company announced last week.
The trial is being conducted in partnership with the nonprofit International AIDS Vaccine Initiative (IAVI). Researchers are testing whether an mRNA-based vaccine that delivers the instructions for HIV-specific antigens can induce certain immune responses.
These antigens, also known as immunogens, were developed by scientific teams at IAVI and Scripps Research. A “proof-of-concept” trial last year found that one of these immunogens generated the desired immune response — priming the right kinds of B cells — in 97 percent of participants.
That trial delivered the priming immunogen itself to the cells. The current trial will use Moderna’s mRNA technology to deliver the genetic instructions for the immunogen, which the cells will then use to make that protein.
In addition, researchers are testing a separate boosting immunogen — also delivered via the mRNA platform — to see if it can help the B cells mature further in the right direction.
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Dr. Mark Feinberg, president and CEO of IAVI, said in a statement.
“The search for an HIV vaccine has been long and challenging, and having new tools, in terms of immunogens and platforms, could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
The new trial, funded in part by the Bill & Melinda Gates Foundation, is the first step in the process of guiding the maturation of certain types of B cells.
The ultimate goal is stimulating the development of B cells that can produce broadly neutralizing antibodies that can target a broad range of HIV variants.
An eventual vaccine using this method will likely involve multiple doses given over weeks to years.
Researchers will enroll 56 healthy, HIV-negative adult volunteers in the current clinical trial. Of these, 48 will receive 1 or 2 doses of the priming immunogen vaccine, with 32 also receiving the boosting immunogen vaccine. Eight people will receive only the vaccine for the boosting immunogen.
In addition, researchers will follow participants for 6 months after their last dose to examine their immune responses and monitor for potential safety concerns.
It has been
Since then, researchers have tried to develop an effective vaccine to protect against HIV — with several large-scale phase 3 clinical trials but no real success.
One challenge with developing an HIV vaccine is that once the virus infects a cell, it replicates wildly, so an effective vaccine would need to essentially block all infection.
“If [HIV] gets through to start an infection, even if somebody has been vaccinated, then that infection is life-long,” said Dr. Davey Smith, an infectious disease specialist and translational research virologist at University of California, San Diego.
Even the COVID-19 vaccines don’t offer this kind of complete protection against infection. However, they still provide strong protection against severe illness, hospitalization, and death.
The bar for an HIV vaccine is higher because of the need to prevent lifelong infection with the virus.
There are effective HIV medicines that can reduce replication of the virus in the body, but they don’t eliminate the virus entirely. These medicines can help people live long and healthy lives and reduce the risk that they will transmit the virus to others.
Earlier attempts at HIV vaccines focused on inducing the immune system to make neutralizing antibodies that inactivate the virus, such as by preventing it from infecting cells.
But HIV evolves rapidly to generate new variants, even more so than the influenza virus.
Each year, the seasonal
In comparison, one study estimates that the worldwide diversity of genetic sequences for the influenza virus is comparable to the diversity of HIV sequences found within a single person with the virus.
The wide genetic variation of HIV makes it difficult to target the virus with a vaccine, because neutralizing antibodies generated in response to one vaccine might work only against a few HIV strains.
More recent HIV vaccine research has focused on developing vaccines than can generate broadly neutralizing antibodies that target parts of the virus’ surface that are the same across many strains.
This is the approach being taken by IAVI and Scripps scientists. The challenge lies in finding the best immunogens to guide the maturation of B cells so they will produce these broadly neutralizing antibodies.
Moderna’s mRNA technology may help speed up this process because much of the work of designing the vaccine can be done on a computer.
This ability helped researchers design candidate COVID-19 vaccines within days of Chinese scientists releasing the genetic sequence of SARS-CoV-2, the coronavirus that causes COVID-19.
“We’ve seen promising proof of concept for germline targeting in [last year’s trial], and this trial lets us take that approach to the next stage,” William Schief, PhD, professor at Scripps Research, said in the statement.
“What’s more, we’ve been able to expedite production of clinical trial material at a remarkably rapid pace because of Moderna’s technology,” he said.
Smith cautions against overhyping the current study, especially with HIV’s ability to evade the body’s immune responses, even those stimulated by vaccines.
“It’s a very, very high hill to climb for this new mRNA technology,” he said, “to generate a very broad and potent immune response to protect against HIV.”
Still, he thinks there’s a lot to gain from this research.
“They set up these trials very smartly, in my opinion, to learn as much as they can,” he said. “What is the immunogen that makes the immune system really rev up? And what is going to help us protect people in the future from HIV exposures?”
He is also thankful for the renewed interest in finding a vaccine for HIV.
While the World Health Organization (WHO) has given HIV an “epidemic” status, many argue that it should be called a “pandemic” because of the millions of people worldwide living with HIV.
“We shouldn’t give up on the last pandemic [HIV] just because we’re fighting the COVID-19 pandemic,” said Smith. “So I really applaud the investigators for looking at new technology to come up with an HIV vaccine, one that we still haven’t gotten even after almost 40 years of trying.”