Moderna is expected to launch a human clinical trial as early as this week for an mRNA-based vaccine against HIV. In a post to ClinicalTrials.gov last week, the company indicated it is looking for 56 people ages 18 to 50 who are HIV-negative. The trial is expected to launch on August 19 and end in the spring of 2023. It is a Phase I study. The company has two HIV vaccine candidates, mRNA-1644 and mRNA-1644v2-Core. Both were tested for safety before use on humans. An HIV vaccine has been something of a Holy Grail for years, with numerous attempts, but many were not found to be safe, and almost none demonstrated anything close to moderate effectiveness. A study of a vaccine in the 2000s run in Thailand reportedly decreased infections by about 30%, but the results are controversial. Another trial in the same period was halted after it seemed to increase the risk of HIV infections. The Moderna and Pfizer-BioNTech COVID-19 vaccines are the first mRNA vaccines authorized for use anywhere in the world. The technology has been in development for at least a decade. A piece of messenger RNA that codes for a part of the virus in question is enfolded into a vector – in the case of the COVID-19 vaccines, a lipid nanoparticle, which is a minuscule ball of fat. Once injected, the mRNA travels inside cells, where the cells’ genetic machinery produces the virus protein — in COVID-19 vaccines, it’s part of the spike protein the virus uses as a key to enter cells. The immune system is then trained to recognize the virus based on that protein so that when it encounters the virus, it attacks it. HIV over the decades has mutated into numerous variants. The mRNA approach is viewed as easily modifiable, which could be an advantage over other vaccine techniques. “The mRNA platform makes it easy to develop vaccines against variants because it just requires an update to the coding sequences in the mRNA that code for the variant,” Rajesh Gandhi, an infectious disease expert who chairs the HIV Medicine Association, told Verywell Health. “Based on its success in protecting against COVID-19, I am hopeful that mRNA technology will revolutionize our ability to develop vaccines against other pathogens, like HIV and influenza.” Other types of vaccine technology use inactive viruses, or in some cases, even live viruses, the so-called “live vaccines.” They often use other less dangerous viruses as vectors and have molecules from the target viruses fused to them in order to train the immune system. mRNA vaccines don’t contain any parts of the virus. So far, the disadvantage to the mRNA vaccines is that mRNA does not last long, so the viruses have to be kept cold to prevent spoilage. In the case of the Pfizer-BioNTech COVID-19 vaccine, it needs to be extremely cold, at about -94 degrees F (-70 degrees C), which requires specialized freezers and transportation. However, they are easily modifiable, which should allow them to be quickly edited to adapt to mutations. HIV, however, is not SARS-CoV-2, the virus that causes COVID-19. HIV infects T-cells, the immune cells that fight viruses and other pathogens, while SARS-CoV-2 primarily infects respiratory cells. mRNA technology may be promising for an HIV vaccine, but only time will tell, although the impact would be enormous. “The only real hope we have of ending the HIV/AIDS pandemic is through the deployment of an effective HIV vaccine, one that is achieved through the work of partners, advocates, and community members joining hands to do together what no one individual or group can do on its own,” wrote Mark Feinberg, president of the International AIDS Vaccine Initiative (IAVI) in June at the 40th anniversary of the HIV epidemic.
