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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
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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
Summary
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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