There was a silver lining to a prophylactic vaccine against hepatitis
C virus (HCV) that failed to prevent chronic HCV infection: it proved
that testing vaccines in a population of patients who inject drugs is
possible, a researcher said here.
A phase I/II randomized trial found no effect on 6-month chronic HCV
outcome among participants randomized to receive HCV vaccine or placebo
(vaccine efficacy -0.529, 95% CI -2.535 to 0.339), reported Andrea Cox,
MD, of Johns Hopkins University in Baltimore.
But the vaccine was well-tolerated, and produced an immunogenic
response in 78% of vaccine recipients (who responded to vaccine peptide
pools in IFN-γ ELISpot assay, which measures T cell response), she
reported in a late-breaking presentation at the
IDWeek
meeting, with joint sponsorship by the Infectious Diseases Society of
America, the Pediatric Infectious Diseases Society, the Society for
Healthcare Epidemiology of America (SHEA), and the HIV Medicine
Association.
Cox painted a dire picture of the global HCV epidemic worldwide,
saying that the chronic rate of both HCV and hepatitis B virus (HBV)
infection is rising.
“If the trend continues as predicted, by 2040, [it is] estimated that
the mortality from HCV and HBV will exceed that of [tuberculosis], HIV,
and malaria combined,” she said.
The World Health Organization is targeting HCV for elimination by
2030, but significant barriers remain, Cox noted. She added that there
are 1.5 million new annual infections globally and the rising rate of
incident infections in the U.S., whereas HBV, a vaccine-preventable
illness, has not shown similar increases.
This vaccine was designed to generate T cell immunity based on viral
vectors, and was comprised of recombinant chimpanzee adenovirus 3 vector
vaccine prime followed by a recombinant modified vaccinia Ankara boost,
both encoding nonstructural proteins of HCV, the authors said.
Participants included adults (ages 18-45) who inject drugs at high
risk of HCV, but who were not infected with HCV at screening. They were
counseled and referred to drug treatment and needle syringe programs,
Cox said. Overall, 455 participants received two injections at 0 and 8
weeks of either vaccine or placebo. Their immune response was assessed
and they were tested for HCV RNA to measure incident infection. They
were followed for 20 months or 9 months following acquisition of
infection.
But the result was the same as it has been for the past 30 years for
people who have been trying to develop a vaccine against HCV, said
Douglas Dieterich, MD, of the Icahn School of Medicine at Mount Sinai in
New York City.
“The positive is they were able to prove you can do a study in this
population of IV drug users at risk for hepatitis C. The bad news is
they haven’t figured out what would work yet. Hepatitis C is a smart
virus,” he told
MedPage Today.
Dieterich, who was not involved in the study, characterized the study
as “a valiant effort, and proof of principle for drug users at high
risk.”
Patients were 78% men, 61% white, and were well-balanced in gender,
race/ethnicity; ILB28 status, age, and BMI were similar in both groups.
The overall incidence of infection was 13 infections per 100 person
years, but there was no difference in incident infection between groups.
For immunogenicity, peak response in the vaccine group was 7 days
following administration of the boost vaccine.
“T-cell responses were induced, but they were less robust and less
broad than in healthy volunteers,” Cox said. “It’s unknown if the
vaccine response is targeting the infecting viruses, but that’s
something we’re now determining.”
Examining safety, there were 79 serious adverse events reported for
65 participants (12%), but none were related to the vaccine regimen, Cox
said. They included endocarditis, trauma, and overdose, which is to be
expected in this population. The most common adverse events in the
vaccine group were tenderness, pain and erythema, or superficial
reddening of the skin. But less than 1% of vaccinated participants
experienced severe reactions, including high-grade local reactions, the
authors said.
Cox emphasized that the need for a vaccine is critical to interrupt
HCV transmission, is significant, and critical to achieve HCV
elimination goals.
“Testing vaccines in [people who inject drugs] is possible, but
additional strategies will need to be considered, ideally with
information gained from this vaccine in informing future vaccine
design,” she said.
The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID).
Page and Cox disclosed no relevant relationships with industry.
Co-authors disclosed support from Gilead and employment with
GlaxoSmithKline and ReiThera.
