A phase 1 clinical trial testing a novel vaccine approach to prevent HIV has produced promising results
The vaccine showed success in stimulating production of rare immune cells needed to start the process of generating antibodies against the fast-mutating virus; the targeted response was detected in 97 percent of participants who received the vaccine.
“We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.” says William Schief, PhD, executive director of vaccine design at IAVI’s Neutralizing Antibody Center, whose laboratory developed the vaccine.
Schief presented the results on behalf of the study team at the International AIDS Society HIV Research for Prevention (HIVR4P) virtual conference.
The study sets the stage for additional clinical trials that will seek to refine and extend the approach—with the long-term goal of creating a safe and effective HIV vaccine.
As a next step, IAVI and Scripps Research are partnering with the biotechnology company Moderna to develop and test an mRNA-based vaccine that harnesses the approach to produce the same beneficial immune cells. Using mRNA technology could significantly accelerate the pace of HIV vaccine development.
One in a million
For decades now, HIV researchers have pursued the holy grail of stimulating the immune system to create rare but powerful antibodies that can neutralize diverse strains of HIV. Known as “broadly neutralizing antibodies,” or bnAbs, these specialized blood proteins could attach to HIV spikes, proteins on the virion surface that allow the virus to enter human cells, and disable them via important yet difficult-to-access regions that don’t vary much from strain to strain.
“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 potential to develop into bnAb-secreting cells,” Schief says. “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.”
The priming step would be the first stage of a multi-step vaccine regimen aimed at eliciting many different types of bnAbs, he says.
Promise beyond HIV
Researchers believe the approach could also be applied to vaccines for other challenging pathogens such as influenza, dengue, Zika, hepatitis C viruses and malaria.
“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.” says Dennis Burton, PhD, director of the NIH Consortium for HIV/AIDS Vaccine Development
The clinical trial, IAVI G001, enrolled 48 healthy adult volunteers.
Participants received either a placebo or two doses of the vaccine compound, eOD-GT8 60mer, along with an adjuvant developed by the pharmaceutical company GSK
“This is a landmark study in the HIV vaccine field, demonstrating success in the first step of a pathway to induce broad neutralizing antibodies against HIV-1,” says Julie McElrath, MD, PhD, director of Fred Hutch’s Vaccine and Infectious Disease Division.