HVTN 302 is another ExMed trial launched in March that has a direct connection to COVID-19. It will test whether the same mRNA technology that was used to deliver genetic instructions for making the SARS-CoV-2 spike protein could be used to deliver, instead, ingredients for making components of three different experimental HIV/AIDS vaccines.
Up to 108 adults who are HIV-negative will be enrolled in the study. The mRNA ingredients of the vaccines will instruct muscle cells near the injection site to produce protein that resemble spikes on HIV, but not the actual virus itself. The hope is that, like the spikes induced by mRNA in COVID-19 vaccines, these HIV spike fragments will stimulate production of HIV antibodies exquisitely tuned to attack the real virus.
“Applying this technology to HIV vaccine research is a defining moment for the field,” said Fred Hutch virologist Larry Corey, MD, in an HVTN Community Compass story marking the launch of the trial.
At the behest of Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, Corey founded HVTN in 1999 and he remains a co-principal investigator of its Fred Hutch-based leadership and operations center.
“We have been studying various HIV vaccines for decades, and the science continues to progress, especially with the major advancements in the COVID-19 vaccines involving the use of mRNA technology,” Corey said.
Testing combinations of vaccine antigens
Another ExMed trial, HVTN 303, will enroll up to 70 participants in a series of steps evaluating up to three different vaccine candidates alone or in combination. Launched in August, the trial is a collaboration involving multiple research centers in the HVTN network, including the University of Pittsburgh and Harvard, although no sites for it have been set up in Seattle.
The first of the three vaccines tested is a so-called fusion peptide conjugate, developed by NIAID’s Vaccine Research Center, that used genetic engineering to create pairs of small proteins that normally appear on HIV surfaces. The vaccines are designed to stimulate antibodies that block those proteins. The trial will also evaluate an adjuvant — an immune-boosting component that can enhance the effectiveness of the primary ingredients. Should this first vaccine and adjuvant show promise, volunteers in the study may test them in various combinations and dosages with two other vaccines. The antigens in those vaccines are made of different dummy proteins that mimic molecular features on HIV’s surface.
“The thing I appreciate about these studies is that we don’t typically look at combinations of vaccines in early phase studies,” said Stephaun Wallace, PhD, MS, principal staff scientist at Fred Hutch and director of external relations for HVTN. “The fact that were doing that in these studies speaks to the rapid pace and step-by-step, or iterative, nature of these trials.”
Elsewhere at Fred Hutch, researchers are studying ways to improve the delivery of HIV prevention interventions so people in need can pick a model that best fits their preferences and might also improve their access to care. The field even has a name, “implementation science,” and Fred Hutch researcher Katrina Ortblad, ScD, MPH, is a trained implementation scientist.
Most of her work is focused on finding ways to improve the delivery of HIV pre-exposure prophylaxis, or PrEP, in which people who do not have HIV — but are at risk of acquiring it — take formulations of antiviral drugs that can protect them from HIV infection.
“When we think about HIV, we have really good tools available, but a lot of people aren’t using them,” Ortblad said. “We have interventions that have been proven to work really well in clinical trials conducted in controlled environments; so now we are working to achieve those same effects in real-world settings, by addressing barriers to access and delivery when things are not as tightly controlled.”