Correlates of Long-term Immune Protection in Hepatitis C Virus (HCV) Exposed Non-reinfected Individuals
The majority of HCV infected individuals develop persistent viremia. Correlates of long-term protective immunity remain undefined. Generation and maintenance of polyfunctional CD4 and CD8 HCV-specific T cells that produce multiple cytokines like IFN-γ, TNF-α and IL-2 correlates with spontaneous resolution of acute primary HCV and can be predictive of long-term protection. The presence of neutralizing antibodies (nAb) was associated with reduced magnitude and length of viremia upon reinfection. The aims of this project were: 1) to define correlates of protective immunity in HCV-resolved high risk people who inject drugs (PWIDs) repeatedly exposed to but resistant to reinfections; and 2) to compare protective immune responses in PWIDs with spontaneous versus treatment-induced clearance. We hypothesized that PWIDs resistant to reinfections harbor an immune response of high magnitude, breadth and quality of the HCV-specific memory T cells as well as higher nAb responses. Using IFN-γ enzyme-linked immunospot (ELISPOT), intracellular staining for cytokines, and pseudoparticle neutralization assays, we examined cellular and humoral immune responses in long-term protected versus reinfected PWIDs. We observed long-lived HCV-specific T cell responses in spontaneously resolved and treatment resolved PWIDs who are protected against reinfection. We did not observe a difference in the nAb responses nor in the functionality of HCV-specific T cells. Our results suggest that protection from reinfection in PWIDs is associated with a sustained high frequency of HCV-specific cellular immune responses.
Vaccins Hepatitis C Virus (HCV) Reinfection Protective Immunity Vaccines People who inject drugs (PWIDs)