The first study of its kind has concluded that although a novel vaccine against hepatitis C does not seem to provide protection against chronic infection with the virus, it elicited immune responses without evidence of safety concerns in an at-risk patient population.
The researchers said they were encouraged by the fact that vaccinated patients demonstrated significantly lower mean peak values of HCV RNA than their unvaccinated counterparts.
“Despite the availability of very effective drugs to treat hepatitis C, we are seeing ongoing infection, largely due to the opioid epidemic,” said Andrea L. Cox, MD, PhD, a professor of medicine at Johns Hopkins University School of Medicine, in Baltimore. “While the global availability of direct-acting antivirals has brought down the number of chronically infected people, new infection rates are high enough so that the net number of infected people has decreased very little in recent years.”
To help address this problem, Dr. Cox and her colleagues evaluated the safety and efficacy of a recombinant chimpanzee adenovirus-3 vectored vaccine in 455 men and women without HCV, who were at risk for infection from active drug use. Participants were randomly assigned to receive the vaccine or two doses of placebo on days 0 and 56 of the trial.
The primary outcome of the study was progression to chronic HCV infection at six months. Secondary outcomes included change in HCV RNA from the incident infection, and peak HCV RNA.
In a presentation at the 2019 annual meeting of the American Association for the Study of Liver Diseases (abstract LP17), Dr. Cox reported that 401 patients were eligible for evaluation: 202 in the vaccinated group and 199 controls who received placebo injections.
The researchers found an overall rate of HCV infection of 13 per 100 person-years, but observed no differences between groups at six months. In each group, 14 patients became chronically infected.
The investigators also found the vaccine to be generally safe and well tolerated, with no serious adverse events related to the inoculation. More vaccinated patients reported adverse events (81%) than those in the placebo group (59%), but these were minor and largely related to the injection, according to the researchers.
Encouragingly, the researchers said, the study revealed significant differences in HCV RNA levels between patients who received the vaccine and placebo, demonstrating that the vaccine induced immune responses and differences in viral trajectory. The researchers also noted that 78% of vaccinated patients mounted T-cell responses to one or more vaccine antigen pools.
“There is clearly a signal here that the vaccine mediated an effect,” Dr. Cox said. “We’re hoping to learn the role of the T cells that suppressed the virus, enhance them, and perhaps add a component that also induces antibody responses. That way, we’ll have both antibody and T-cell control of the virus.”
The researchers hope the study will be a springboard for a vaccine that ultimately prevents HCV infection.
“I think the immediate next step is to learn what we can from this trial to design better vaccines,” Dr. Cox said. “This signal is helpful in that we may be able to get an idea of what an effective T-cell response looks like, maximize that, and combine it with something that induces antibodies.”
Arthur Y. Kim, MD, an associate professor of medicine at Harvard Medical School, in Boston, agreed that despite the availability of excellent treatments, the elimination of hepatitis C will likely require a vaccine.
“While development of a vaccine is badly needed, unfortunately there hasn’t been enough investment in HCV vaccine research, so it may be some time before one is available for widespread use,” Dr. Kim said. “Right now, we are seeing rising rates of all sorts of infections related to injections, including HCV. An HCV vaccine would be part of a comprehensive bundle to prevent viral and bacterial infections, which are of great threat to the individual and costly to the health care system.”
—Michael Vlessides
Drs. Cox and Kim reported no relevant financial conflicts of interest.