An experimental two-part vaccine was not able to
prevent chronic hepatitis C virus (HCV) infection in a mid-stage study, according
to a presentation at the recent IDWeek 2019 conference in Washington, DC.
Prof.
Andrea Cox of Johns Hopkins University reported that study participants who
received the prime-boost vaccine were no less likely to develop chronic
infection than placebo recipients, but they did show stronger immune responses against the virus.
Successful treatment of hepatitis C reduces new
infections, as people who are cured can no longer transmit the virus. But despite
a dramatic improvement in the cure rate since the advent of direct-acting
antivirals, many experts believe that the World Health Organization goal of eliminating
hepatitis C as a global public health threat can only be
achieved with a vaccine.
Yet efforts to develop an effective HCV vaccine have
been hampered by several challenges including the high variability of the virus – which has also stymied HIV vaccine development – and incomplete natural
immunity.
Around a quarter of people with acute HCV infection are able to clear the virus
spontaneously without treatment, while the remainder develop chronic, or
long-term infection lasting more than six months. Unlike
hepatitis A and B, people who clear hepatitis C naturally or are cured with antivirals
can become infected again. However, those who are infected a second time typically have
lower HCV viral load. And, as Cox explained at the 2016 International Symposium on
Hepatitis Care in Substance Users in Oslo, the magnitude and breadth of
T-cell responses increase and the likelihood of spontaneous clearance rises
with each subsequent infection.
At
IDWeek, Cox presented findings from a phase I/II clinical trial (NCT01436357) evaluating
a dual prime-boost vaccine strategy for HCV prevention.
The
vaccine regimen involves a recombinant chimpanzee adenovirus 3 vector prime
vaccine (known as AdCh3NSmut1) followed by a recombinant modified vaccinia Ankara
booster (MVA-NSMut
HCV), both genetically engineered to encode nonstructural proteins from
genotype 1b HCV.
The study included 455 participants age 18 to 45 who were at risk for HCV
through injection drug use. Nearly 80% were men and about 60% were white. They were enrolled at Johns Hopkins
in Baltimore, the University of California at San Francisco and the University
of New Mexico.
Participants
were randomly assigned to receive the prime-boost regimen or placebo injections
administered at the start of the study and eight weeks later. The researchers
monitored vaccine safety, immunogenicity (ability to stimulate immune responses)
and ability to prevent chronic HCV infection.
The overall incidence of HCV infection
after six months of follow-up was 13 cases per 100 person-years, Cox reported. She
noted that this was lower than expected, likely because study participants in
both arms received counselling and referral to syringe programmes, addiction
treatment and other harm reduction services.
However,
the study found no difference between vaccine and placebo arms in the likelihood
of developing chronic infection, with 14 cases in both groups.
The
vaccine did seem to stimulate immune responses against the virus. Among the
participants who received the active vaccine, 78% generated T-cell responses to
at least one of the encoded HCV antigens. And people who became infected in
this group had lower peak HCV viral load, on average.
The
vaccine combination was generally safe and well tolerated, Cox said, with no
serious vaccine-related adverse events. More people who received the active
vaccine reported adverse events compared with placebo recipients (81% vs 59%),
mostly attributable to injection site reactions.
The vaccine candidate "elicited robust immune responses without evident
safety concerns, but did not provide protection against chronic HCV
infection," the researchers concluded, adding that this study demonstrates
the feasibility of conducting rigorous vaccine research among people who inject
drugs.