Cloning of the first human anti-JCPyV/vp1 neutralizing monoclonal antibody: Epitope definition and implications in risk stratification of patients under natalizumab therapy

0440363 - MBÚ 2015 RIV NL eng J - Článek v odborném periodiku
Diotti, R.A. - Mancini, N. - Clementi, N. - Sautto, G. - Moreno, G.J. - Criscuolo, E. - Cappalletti, F. - Man, Petr - Forest, E. - Remy, L. - Giannecchini, S. - Clementi, M. - Burioni, R.
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. Roč. 108, č. 2 (2014), s. 94-103. ISSN 0166-3542. E-ISSN 1872-9096
Institucionální podpora: RVO:61388971
Klíčová slova: natalizumab * JC virus * multiple sclerosis
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 3.938, rok: 2014

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.
Trvalý link: http://hdl.handle.net/11104/0243472