HCV vaccine candidates have been yielded by the virus genome's high genetic variability, and lacking suitable animal models.
Many recent advancements in the treatment of hepatitis C virus (HCV), especially the availability of direct acting antivirals (DAAs), have resulted in short treatment duration, high cure rates, and minimal side effects for patients infected with HCV.
The main drawbacks of DAA therapy include the high treatment cost (up to $147,000 for 1 course of therapy) and the inability of the treatment to prevent reinfection — especially in high risk populations such as intravenous drug users.
Researchers believe that the long-term solution lies in a vaccine to prevent HCV — especially in high risk groups, where an effective vaccine has been projected to prevent infection in 50% to 80% of recipients.
Makutiro Masavuli, a PhD candidate at the University of Adelaide in Australia whose research is currently focused on the development of an HCV vaccine, reviewed potential candidates in preclinical development for an HCV vaccine in an article published last month.
There are several reasons why there has been no successful HCV vaccines to date, including both the high genetic variability of the virus genome and the unavailability of “suitable small animal models that can mimic HCV infection of humans,” the researchers noted.
In addition, many traditional methods of vaccine development, such as using a killed or live-attenuated HCV, carry too much risk to be tested and used in humans.
“These shortcomings have led to the development of experimental vaccines which include DNA vaccines, recombinant (non-pathogenic) vectors, proteins and virus like particles (VLPs),” researchers wrote. “Despite the many obstacles that impede the development of these vaccines, several studies involving VLP-based vaccine candidates have already generated promising results in preclinical studies.”
Scientists have looked at numerous potential starting points for an HCV VLP vaccine, including HCV, hepatitis B virus (HBV), murine leukemia virus (MLV), recombinant vesicular stomatitis virus (rVSV), and papaya mosaic virus (PapMV).
When developing an effective HCV vaccine, researchers must also consider the method of producing the desired VLP. Potential production systems include bacteria (Escherichia coli), yeast (Saccharomyces cerevisiae and Pichia pastoris), mammalian cells, plant cells (tobacco and lettuce leaves), and insect cells (the baculovirus expression vector/insect cell or BEVS/IC system).
The BEVS/IC system is especially promising, as one of the two currently available human papillomavirus (HPV) vaccines (Cervarix) was developed and produced using this system. The biggest drawbacks of the BEVS/IC system are the high cost and difficulty in scaling up the procedure for manufacture of a vaccine product.
Masavuli concluded that the path to a HCV vaccine is yielded by the virus’ virulent nature and its evasiveness to immune responses.
“However, advances in technology and our understanding of the natural course of HCV infection, the pathogenetic mechanisms, and the immunological markers which correlate with resolution of infection or protection, provide useful information for vaccine design,”researchers wrote.
The article, “Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C,” was published online in Frontiers in Microbiology last month.