Abstract
Hepatitis C virus (HCV) can be cleared naturally in a subset of individuals. However, the asymptomatic nature of acute HCV infection makes the study of the early immune response and defining the correlates of protection challenging. Despite this, there is now strong evidence implicating the humoral immune response, specifically neutralising antibodies, in determining the clearance or chronicity outcomes of primary HCV infection. In general, immunoglobulin G (IgG) plays the major role in viral neutralisation. However, there are limited investigations of anti-HCV envelope protein 2 (E2) isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1–4) in early HCV infection. In this study, using a rare cohort of 14 very recently HCV-infected individuals (4–45 days) with varying disease outcome (n = 7 clearers), the timing and potency of anti-HCV E2 isotypes and IgG subclasses were examined longitudinally, in relation to neutralising antibody activity. Clearance was associated with anti-E2 IgG, specifically IgG1 and IgG3, and appeared essential to prevent the emergence of new HCV variants and the chronic infection outcome. Interestingly, these IgG responses were accompanied by IgM antibodies and were associated with neutralising antibody activity in the subjects who cleared infection. These findings provide novel insights into the early humoral immune response characteristics associated with HCV disease outcome.
Highlights
Hepatitis C virus (HCV) is a major cause of chronic liver disease globally [1,2]
These immunoglobulin G (IgG) responses were accompanied by immunoglobulin M (IgM) antibodies and were associated with neutralising antibody activity in the subjects who cleared infection
These findings provide novel insights into the early humoral immune response characteristics associated with HCV disease outcome
Summary
Hepatitis C virus (HCV) is a major cause of chronic liver disease globally [1,2]. It is predominantly transmitted via blood-to-blood contact associated with injecting drug use (IDU), via sharing of injecting equipment [3,4]. While direct-acting antiviral (DAAs) treatments are decreasing the number of people living with HCV, control remains challenging globally due to the limitations in health infrastructure and high drug cost for treatment of the marginalised population affected, in addition to high rates of re-infection [8,9,10,11,12,13]. As HCV can be cleared naturally in a subset of individuals (~25%), and as subsequent re-infections are characterised by higher clearance rates (up to ~80%), it is reasonable to hypothesise that a vaccine could be designed to elicit effective immune responses that confer protection [14,15].
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