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JC polyomavirus mutants escape antibody-mediated neutralization

Upasana Ray1, Paola Cinque2, Simonetta Gerevini3

  • 1Lab of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Science Translational Medicine
|September 25, 2015
PubMed

Insights

JC polyomavirus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. JCV VP1 mutations in PML patients evade antibodies, but JCV virus-like particle (VLP) vaccination may restore neutralizing immunity and prevent PML.

Area of Science:

  • Virology
  • Immunology
  • Neuroscience

Background:

  • JC polyomavirus (JCV) establishes persistent infections in the adult urinary tract.
  • Immune suppression can lead to JCV-associated opportunistic brain disease, progressive multifocal leukoencephalopathy (PML).
  • JCV strains from PML patients exhibit mutations in the major capsid protein (VP1) surface loops.

Purpose of the Study:

  • To investigate if VP1 mutations in JCV strains from PML patients contribute to immune evasion.
  • To assess the potential of JC polyomavirus virus-like particle (VLP) vaccination in overcoming neutralizing antibody deficiencies.

Main Methods:

  • Neutralization serology was performed on plasma samples from PML patients and healthy individuals against wild-type and PML-mutant JCV strains.
  • Mice were immunized with JCV VLPs to assess the development and closure of neutralizing "blind spots".
  • A PML patient received an experimental JCV VLP vaccine, and neutralizing titers against cognate PML-mutant JCV were measured.

Main Results:

  • Plasma from PML patients failed to neutralize patient-cognate PML-mutant JCV strains, unlike wild-type JCV.
  • Healthy individuals' plasma generally cross-neutralized all tested JCV variants.
  • Mice showed initial neutralizing "blind spots" that resolved after booster immunizations.
  • The PML patient exhibited a significantly increased neutralizing titer against her PML-mutant JCV after VLP vaccination.

Conclusions:

  • Deficient humoral immunity against specific JCV variants is a common feature in PML pathogenesis.
  • JC polyomavirus VLP vaccination can enhance neutralizing antibody responses, potentially overcoming humoral deficiencies.
  • JCV VLP vaccination holds promise as a strategy to prevent PML development.

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