Earlier this year, Moderna started a small human trial of a vaccine against HIV infection using the same mRNA technology that led to the success and rapid availability of COVID-19 vaccines. They expect to have safety data (and some hints about effectiveness) in 2023.
mRNA technology has been in development for decades, and we can consider ourselves extremely lucky that it was ready to deploy for the first time when the pandemic arrived. We can expect mRNA technology to become more common in other vaccines.
Moderna has developed three closely related mRNA vaccines against HIV and is currently in Phase I clinical trials in humans. The trial began enrolling volunteers in February and is expected to be complete by October 2023.
108 study subjects are being randomly assigned to get one of three different candidate vaccines. They’re testing a 3-dose vaccine series. The second shot is at month 2 and the third shot is at month 6. The primary endpoint (aka main metric) of this study is to test vaccine safety. Participants will be monitored closely for severe reactions. A secondary aim, however, is to do blood tests for neutralizing HIV antibodies in participants.
HIV has been a tricky one in terms of a vaccine. All vaccines basically work the same way: they teach the immune system to recognize a particular pathogen. Once recognized, the immune system can neutralize the threat before it has a chance to infect us again. Or at least, dampen the infection.
However, HIV is a little different. First of all, it mutates a lot, so it’s hard to figure out exactly what to teach the immune system to recognize. Also, since HIV causes a chronic infection (you’re infected for life), we don’t have any good examples of what neutralizing antibodies might look like. There is no naturally acquired immunity that we can try to make a vaccine replicate.
History of Vaccines puts it like this: “Because no one is known to have been infected with HIV and then naturally cleared the virus, we do not know what protection from HIV would look like in a person. Would it be production of a certain kind and number of antibodies? Would it be the persistence of a certain kind of memory T cell? Until researchers have established what the correlates of protective immunity to HIV infection are, designing and validating a vaccine will be difficult.”
Finally, though many HIV vaccines have been tested in animals, so far their performance in animal models has not been a good predictor of how the same vaccines perform in humans. This really slows down the vaccine development process.
In 2009, a large human vaccine trial (known as “the Thai trial” because it was fielded in Thailand) tested a combo vaccine that was 31% effective at preventing HIV infection. However, 31% efficacy isn’t considered good enough to deploy at the population level. Many lessons were learned from the Thai trial–including, for the first time, what it looks like to be immunized against HIV. Moderna is capitalizing on those lessons as well as new mRNA technology to create and test new options.
Fingers crossed on this one!