After years of effort, researchers are reporting that there were encouraging results from a phase 1 clinical trial that tested a new approach toward HIV vaccination. The vaccine was able to trigger the production of a rare type of immune cell that can initiate the process of making antibodies against HIV, which is known for its ability to rapidly mutate (and evade the immune system). This response was seen in 97 percent of volunteers who received the vaccine.
"This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well," said William Schief, Ph.D., a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI's Neutralizing Antibody Center, whose laboratory created the vaccine. "With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties, and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens."
The results were presented at the virtual meeting of the International AIDS Society HIV Research for Prevention (HIVR4P). Further clinical trials can now be planned so that the vaccine can be improved and refined. IAVI and Scripps Research are also now working with Moderna to research whether mRNA technology can accelerate HIV vaccine development.
Though there are treatment options that can reduce the risk of spreading an HIV infection and it's no longer a death sentence, HIV still impacts over 38 million people globally.
Scientists have been trying to figure out how to coax the immune system to generate antibodies that can neutralize different strains of HIV since it can mutate so easily. These are known as broadly neutralizing antibodies (bnAbs) and they can bind to the spike protein of HIV, which HIV uses to enter potential host cells. If these spike proteins are neutralized, infection is prevented, and often the spike protein doesn't change much from one HIV strain to another.
"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 [the] potential to develop into bnAb-secreting cells," Schief explained. "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."
Priming the immune system would be a first step in what would be a multi-step regimen for vaccination, and would hopefully trigger the production of many kinds of bnAbs. This approach might be useful for creating vaccines against other challenging viruses like dengue and malaria. When the rare, naive B cells are targeted in a specific way it's called germline targeting; they display antibodies that are encoded by unmodified or germline genes.
"This is a tremendous achievement for vaccine science as a whole," added Dennis Burton, Ph.D., Professor and Chair of the Department of Immunology and Microbiology at Scripps Research, Scientific Director of the IAVI Neutralizing Antibody Center, and Director of the NIH Consortium for HIV/AIDS Vaccine Development. "This clinical trial has shown that we can drive immune responses in predictable ways to make new and better vaccines, and not just for HIV. We believe this type of vaccine engineering can be applied more broadly, bringing about a new day in vaccinology."