{
  "abstract": "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 T 1 (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 T 1 (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.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Ana Luz Chumbe"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Suzanne M D van den Aardweg"
    },
    {
      "affiliations": [
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands",
        "Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, Netherlands",
        "Stichting HIV Monitoring, Amsterdam, Netherlands",
        "Department of Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands"
      ],
      "name": "Anders Boyd"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Marloes Grobben"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Sylvie M Koekkoek"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Ian Zon"
    },
    {
      "affiliations": [
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands",
        "Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, Netherlands",
        "Department of Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands"
      ],
      "name": "Maria Prins"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Kwinten Sliepen"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Marit J van Gils"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands",
        "Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands"
      ],
      "name": "Janke Schinkel"
    }
  ],
  "title": "Characteristics of an antibody profile associated with protection against hepatitis C virus reinfection in a high-risk cohort",
  "uid": "4367bf63-6f66-53e9-972f-2fde03cae596"
}