ABSTRACT
Given the global disease burden and public health impact of hepatitis C, the development
of an effective vaccine is of paramount importance. However, many challenging obstacles
loom ahead of this goal. The hepatitis C virus (HCV), being an RNA virus, can mutate
rapidly in adaptation to the environment, thus contributing to the high sequence divergence
of multiple viral isolates in the world. The highest heterogeneity has been found
in the hypervariable region of the envelope glycoprotein 2, which contains a principal
neutralization epitope. HCV also causes persistent infection in a high percentage
of immunocompetent hosts despite active immune response. The lack of an efficient
tissue culture system for propagating HCV and testing neutralizing antibodies adds
further complexity to the task of vaccine development. The immunologic correlates
associated with disease progression or protection are yet to be defined, but recent
studies suggest that a vigorous multispecific cellular immune response is important
in the resolution of infection. Induction of high-titer, long-lasting, and cross-reactive
antienvelope antibodies and a vigorous multispecific cellular immune response that
includes both helper and cytotoxic T lymphocytes may be necessary for an effective
vaccine. Several promising approaches have been used to develop an HCV vaccine. Novel
vaccine candidates based on molecular technology such as recombinant proteins, peptides,
viruslike particles, naked DNA, and recombinant viruses are being explored. The final
vaccine product may require multiple components that target various aspects of protective
immunity. Finally, sterilizing immunity may not be necessary if a vaccine can be developed
to prevent chronic infection, which is the major cause of morbidity and mortality
from this disease.
KEYWORD
recombinant subunit vaccine - immune response - cytotoxic T cell - T helper cell -
antibody - protective immunity
