Gut · 2025
Characteristics of an antibody profile associated with protection against hepatitis C virus reinfection in a high-risk cohort.
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Chumbe Ana Luz, van den Aardweg Suzanne M D, Boyd Anders, Grobben Marloes, Koekkoek Sylvie M, Zon Ian, Prins Maria, Sliepen Kwinten, van Gils Marit J, Schinkel Janke
Аннотация
BACKGROUND: Without a vaccine, HCV (re)infections continue to afflict individuals at high risk, for example, men who have sex with men (MSM).
OBJECTIVE: To guide vaccine development, we assessed whether natural protection against observed HCV reinfection among MSM was associated with a distinct humoral immune profile.
DESIGN: From a prospective cohort of HIV-positive MSM with acute HCV infection (MOSAIC, Dutch MSM Observational Study of Acute Infection with hepatitis C), we selected 13 cases who became HCV-reinfected (R) and 18 controls who remained free of observed reinfections (non-reinfected, NR) in 0.5-9.5 years after primary infection clearance, matched for calendar year of primary infection. At time point T1 (29 days before to 78 days after primary clearance) and T2 (3-6 months before R subjects' first reinfection), we evaluated serum antibody responses against HCV's E1E2 envelope glycoprotein. Based solely on E1E2-binding antibody levels and Fc-gamma receptor (FcγR)/C1q engagement at T1, we divided participants into subgroups using latent profile analysis.
RESULTS: HCV-neutralising responses were observed mainly at T1 (9/18 NR and 3/13 R participants). The NR group could be distinguished from the R group at T1 by higher levels of E1E2-binding antibodies that bound FcγRs/C1q. Among four identified latent profiles, HCV reinfection prevalence was lowest in the profile defined by moderate to high levels of E1E2-binding antibodies (IgM/IgG/IgG1/IgG3) and FcγR/C1q engagement. This profile exhibited a relatively broad, potent HCV-neutralising capacity and the broadest epitope specificity.
CONCLUSION: We propose broad, potent serum Fc-mediated effector functions and neutralisation and a broad anti-E1E2 antibody epitope specificity as ingredients of HCV-protective immunity towards which vaccination approaches should aim.
OBJECTIVE: To guide vaccine development, we assessed whether natural protection against observed HCV reinfection among MSM was associated with a distinct humoral immune profile.
DESIGN: From a prospective cohort of HIV-positive MSM with acute HCV infection (MOSAIC, Dutch MSM Observational Study of Acute Infection with hepatitis C), we selected 13 cases who became HCV-reinfected (R) and 18 controls who remained free of observed reinfections (non-reinfected, NR) in 0.5-9.5 years after primary infection clearance, matched for calendar year of primary infection. At time point T1 (29 days before to 78 days after primary clearance) and T2 (3-6 months before R subjects' first reinfection), we evaluated serum antibody responses against HCV's E1E2 envelope glycoprotein. Based solely on E1E2-binding antibody levels and Fc-gamma receptor (FcγR)/C1q engagement at T1, we divided participants into subgroups using latent profile analysis.
RESULTS: HCV-neutralising responses were observed mainly at T1 (9/18 NR and 3/13 R participants). The NR group could be distinguished from the R group at T1 by higher levels of E1E2-binding antibodies that bound FcγRs/C1q. Among four identified latent profiles, HCV reinfection prevalence was lowest in the profile defined by moderate to high levels of E1E2-binding antibodies (IgM/IgG/IgG1/IgG3) and FcγR/C1q engagement. This profile exhibited a relatively broad, potent HCV-neutralising capacity and the broadest epitope specificity.
CONCLUSION: We propose broad, potent serum Fc-mediated effector functions and neutralisation and a broad anti-E1E2 antibody epitope specificity as ingredients of HCV-protective immunity towards which vaccination approaches should aim.