Serum Antibodies Against the Oncogenic Merkel Cell Polyomavirus Detected by an Innovative Immunological Assay With Mimotopes in Healthy Subjects

• Published in: Frontiers in immunology Vol. 12; p. 676627
• Main Authors: Mazziotta, Chiara, Lanzillotti, Carmen, Torreggiani, Elena, Oton-Gonzalez, Lucia, Iaquinta, Maria Rosa, Mazzoni, Elisa, Gaboriaud, Pauline, Touzé, Antoine, Silvagni, Ettore, Govoni, Marcello, Martini, Fernanda, Tognon, Mauro, Rotondo, John Charles
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 08.06.2021; Frontiers Media S.A
• Subjects: Adult; antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Asymptomatic Infections; Cancer; Capsid Proteins - immunology; Computer Simulation; Data Accuracy; Diagnosis, Computer-Assisted; Enzyme Assays - methods; Enzyme-Linked Immunosorbent Assay - methods; Epitopes - immunology; Female; Healthy Volunteers; Humans; IgGs; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunology; indirect ELISA; Life Sciences; Male; MCPyV; Merkel cell polyomavirus; Merkel cell polyomavirus - immunology; Microbiology and Parasitology; Middle Aged; Oncogenic Viruses - immunology; Polyomavirus Infections - blood; Polyomavirus Infections - diagnosis; Polyomavirus Infections - virology; Sensitivity and Specificity; Seroepidemiologic Studies; serology; Tumor Virus Infections - blood; Tumor Virus Infections - diagnosis; Tumor Virus Infections - virology; Virology; polyomavirus; indirect ELISA; Merkel cell carcinoma; serology; IgGs; antibodies; MCPyV; Merkel cell polyomavirus
• DOI: 10.3389/fimmu.2021.676627
• ISSN: 1664-3224

Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, has been detected in Merkel cell carcinoma (MCC) and in normal tissues. Since MCPyV infection occurs in both MCC-affected patients and healthy subjects (HS), innovative immunoassays for detecting antibodies (abs) against MCPyV are required. Herein, sera from HS were analyzed with a novel indirect ELISA using two synthetic peptides mimicking MCPyV capsid protein epitopes of VP1 and VP2. Synthetic peptides were designed to recognize IgGs against MCPyV VP mimotopes using a computer-assisted approach. The assay was set up evaluating its performance in detecting IgGs anti-MCPyV on MCPyV-positive (n=65) and -negative (n=67) control sera. Then, the ELISA was extended to sera (n=548) from HS aged 18-65 yrs old. Age-specific MCPyV-seroprevalence was investigated. Performance evaluation indicated that the assay showed 80% sensitivity, 91% specificity and 83.9% accuracy, with positive and negative predictive values of 94.3% and 71%, respectively. The ratio expected/obtained data agreement was 86%, with a Cohen’s kappa of 0.72. Receiver-operating characteristic (ROC) curves analysis indicated that the areas under the curves (AUCs) for the two peptides were 0.82 and 0.74, respectively. Intra-/inter-run variations were below 9%. The overall prevalence of serum IgGs anti-MCPyV in HS was 62.9% (345/548). Age-specific MCPyV-seroprevalence was 63.1% (82/130), 56.7% (68/120), 64.5% (91/141), and 66.2% (104/157) in HS aged 18-30, 31-40, 41-50 and 51-65 yrs old, respectively (p>0.05). Performance evaluation suggests that our indirect ELISA is reliable in detecting IgGs anti-MCPyV. Our immunological data indicate that MCPyV infection occurs asymptomatically, at a relatively high prevalence, in humans.