Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.

Abstract : JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment.
Type de document :
Article dans une revue
Antiviral Research, Elsevier Masson, 2014, 108, pp.94-103
Liste complète des métadonnées

http://hal.univ-grenoble-alpes.fr/hal-01130590
Contributeur : Frank Thomas <>
Soumis le : jeudi 12 mars 2015 - 09:10:31
Dernière modification le : mercredi 21 mars 2018 - 18:57:46

Identifiants

  • HAL Id : hal-01130590, version 1
  • PUBMED : 24909571

Collections

Citation

Roberta Antonia Diotti, Nicasio Mancini, Nicola Clementi, Giuseppe Sautto, Guisella Janett Moreno, et al.. Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.. Antiviral Research, Elsevier Masson, 2014, 108, pp.94-103. 〈hal-01130590〉

Partager

Métriques

Consultations de la notice

453