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.
| Original language | English |
|---|---|
| Pages (from-to) | 94-103 |
| Number of pages | 10 |
| Journal | Antiviral Research |
| Volume | 108 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- JCPyV
- Monoclonal antibody
- Multiple sclerosis
- Natalizumab
- Neutralizing activity
- Progressive multifocal leukoencephalopathy (PML)
ASJC Scopus subject areas
- Virology
- Pharmacology
- Medicine(all)
Cite this
Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody : Epitope definition and implications in risk stratification of patients under natalizumab therapy. / Diotti, Roberta Antonia; Mancini, Nicasio; Clementi, Nicola; Sautto, Giuseppe; Moreno, Guisella Janett; Criscuolo, Elena; Cappelletti, Francesca; Man, Petr; Forest, Eric; Remy, Louise; Giannecchini, Simone; Clementi, Massimo; Burioni, Roberto.
In: Antiviral Research, Vol. 108, No. 1, 2014, p. 94-103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody
T2 - Epitope definition and implications in risk stratification of patients under natalizumab therapy
AU - Diotti, Roberta Antonia
AU - Mancini, Nicasio
AU - Clementi, Nicola
AU - Sautto, Giuseppe
AU - Moreno, Guisella Janett
AU - Criscuolo, Elena
AU - Cappelletti, Francesca
AU - Man, Petr
AU - Forest, Eric
AU - Remy, Louise
AU - Giannecchini, Simone
AU - Clementi, Massimo
AU - Burioni, Roberto
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - JCPyV
KW - Monoclonal antibody
KW - Multiple sclerosis
KW - Natalizumab
KW - Neutralizing activity
KW - Progressive multifocal leukoencephalopathy (PML)
UR - http://www.scopus.com/inward/record.url?scp=84903170770&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903170770&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2014.05.017
DO - 10.1016/j.antiviral.2014.05.017
M3 - Article
C2 - 24909571
AN - SCOPUS:84903170770
VL - 108
SP - 94
EP - 103
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 1
ER -