Moderna is beginning human trials on its experimental mRNA-based HIV vaccine, possibly this week, according to a recent submission to the U.S. National Institutes of Health Clinical Trial registry.
In other words, we might be approaching the horizon of one of the worst illnesses of the last hundred years.
Moderna's Phase 1 HIV vaccine trial will last 10 months
Moderna's Phase 1 trial will reportedly include 56 healthy (HIV-free) adults who are 18 to 50 years old. The first phase aims to evaluate the safety of the vaccine, in addition to observing how human immune responses develop. Functionally similar to the pharmaceutical company's COVID-19 vaccine, the newest one is also an mRNA-based candidate. And this comes on the heels of years of research into the potential of mRNA vaccines, with Moderna and Pfizer's becoming the world's first such vaccines used in humans, which have proved generally successful in reducing the severity and outright preventing COVID-19 coronavirus infections.
Notably, Moderna will trial two different versions of its novel vaccine candidate, called mRNA-1644 (or mRNA-1644v2-Core), and it marks the first-ever mRNA vaccine designed to take down HIV to see human trials. Four groups will participate in the trials, two of which will receive mixes of the different versions, and the other two receiving the other variant. As of writing, the trial is not a blind one, which means everyone who gets the real deal will know it. This is because the researchers aren't studying the effectiveness of the vaccine, at this point, with the first phase lasting roughly 10 months just to test the safety and reliability of immune response.
Moderna's mRNA candidate could be key to an early immune response
Once the vaccine completes the initial phase of testing, the researchers will still have a long road to official approval. Phases 2 and 3 will focus on analyzing the vaccine's effectiveness in preventing HIV infection for the wider population. But it has a good chance of seeing impressive results, especially since it's an mRNA vaccine. These break with the traditional kind, which typically includes a weakened or inactivated virus, by delivering a "cheat sheet" to our cells that shows them how to create fragments of specific proteins that rest on the exterior of a targeted virus.
After vaccine injection, our cells begin to create these proteins for roughly 24 to 48 hours, which our bodies identify as foreign, thus triggering an immune response. The aim is for the body to be prepared to recognize the spike proteins when the real virus arrives, enabling it to mount a rapid response to defeat the infection before it can spread into a severe case. "The hypothesis is that sequential vaccination by a germline-targeting prime followed by directional boost immunogens can induce specific classes of B-cell responses and guide their early maturation toward broadly neutralizing antibody (bnAb) development through an mRNA platform," read Moderna's clinical trial submission. In other words, it's crucial to stimulate broadly neutralizing antibodies (bnAbs) to effectively defend against HIV.
Historically, curating vaccines for HIV has remained difficult because of how quickly it infects human DNA, mutating its structure. While the most promising method involved stimulating broadly neutralizing antibodies, scientists have struggled to trigger this reaction with a vaccine, but the new mRNA candidate vaccine might make a difference. Earlier this year, the International AIDS Vaccine Initiative and Scripps Research tested a snippet of the mRNA HIV vaccine candidate (the immunogen), and, while the full immune response didn't happen, 97% of study participants still developed the intended immune response, stimulating B cells in an early target window. We have a long way to go before we can successfully fight off HIV, but the horizon might be in sight.