Experts in a recent review stated that an effective hepatitis C vaccine is critical for significant global control of the infection in combination with increased screening and treatment.
However, there are several barriers to HCV vaccine development, including virus diversity, limited models for testing vaccines, and incomplete understanding of protective immune responses.
“Although pharmaceutical companies invest in drug development, vaccine development requires investment from sources beyond government and charitable foundations,” Justin R. Bailey, MD, PhD, from the Johns Hopkins University School of Medicine in Maryland, and colleagues wrote. “A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge.”
HCV genetic diversity presents one of the principal challenges for vaccine development, considering there are seven known genotypes — and a possible eighth recently discovered — with more than 80 subtypes. Additionally, immune selection and error-prone polymerase of the virus generate “a diverse quasispecies of related but genetically distinct viral variants” in individuals, according to Bailey and colleagues.
Another barrier to HCV vaccine development is the lack of in vitro or animal models available to determine whether a vaccine induces protective immunity.
“Direct infusion of HCV-infected human plasma might be considered, but would require careful screening for other pathogens and, even with thoughtful selection of inoculum levels and HCV genotypes, might fail to completely recapitulate natural exposure,” the researchers wrote. “Although our incomplete understanding of protective immunity against HCV is a barrier to vaccine development, studies have provided substantial evidence that protective immunity does exist.”
Regarding spontaneous clearance of HCV, both chimpanzees and humans have demonstrated recurrent HCV viremia following additional HCV exposure after initial control. This, according to the researchers, shows that spontaneous clearance of primary HCV does not generate sterilizing immunity.
However, previous studies have reported clearance of multiple infections with homologous and heterologous viruses in chimpanzees and humans. Rapid and effective control of viral replication with subsequent exposures indicates that adaptive immunity is induced and protects against chronic infection.
“Additional research on effective immune control of HCV is needed to develop a vaccine, including studies of people with repeated spontaneous control of diverse HCV infections over time,” Bailey and colleagues wrote. “Vaccine strategies meant to overcome the enormous diversity of HCV must generate a broad immune response, capable of responding to abundant variations. Selecting antigens to maximize the induction of T-cell and antibody responses that elicit successful responses remains an active area of research.” – by Talitha Bennett
Disclosure: HCV Next was unable to determine the authors’ relevant financial disclosures at the time of publication.