Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

Abstract

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.

Hepatitis C virus: A critical approach to who really needs treatment

“…The protection provided was no greater than that provided by the placebo[ 112 ]. Recent investigation on HCV vaccine adjuvants demonstrated that the induction of a strong T and B cell immunity is enhanced by choosing the right adjuvant[ 113 ]. The subject of vaccines producing neutralizing antibodies has also been briefly reviewed in two recent editorials[ 114 , 115 ].…”

In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?

“…Unfortunately, a phase I/II study in PWID population showed that this vaccination strategy was not effective for preventing chronic infections since T cell exhaustion was not reversed (ClinicalTrials.gov Identifier: NCT01436357[ 193 ])[ 194 , 230 ]. These results highlight the need for a vaccine strategy that stimulates both humoral and T cell immunity[ 23 , 231 ]. However, attempts to enhance CMI without the need of boosting the generation of Abs, have been addressed in pre-clinical studies on non-human primates by fusing the HCV non-structural antigen to MHC class II-associated invariant chain[ 232 ].…”

“…When NS3 DNA vaccine was co-administered with interleukin-12 as adjuvant, strong immunogenicity was also displayed in murine models[ 258 ]. Several other adjuvants have also been employed in NS3-based DNA vaccination in order to enhance their potency (for a detailed review see Sepulveda-Crespo et al [ 231 ] 2020). In addition, constructs encoding a codon-optimized NS5A injected IM into mice, in combination with in vivo electroporation, were also able to prime specific T cell responses[ 259 ].…”

Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial

“…Alternatively, advances in vaccine adjuvant, immunopotentiator, and vaccine particle development offer the potential to trigger multiple immune pathways with a single vaccine platform, such as recombinant protein antigens that with certain adjuvants not only trigger robust B cell and CD4 + T cell responses but also induce cross-presentation to CD8 + T cells. Numerous such platforms are being actively evaluated in pre-clinical and limited clinical studies of new HCV vaccines, and recent reviews have examined this in more comprehensive detail [ 113 , 114 ].…”