Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients

Journal of Translational Medicine

Research

Luigi Buonaguro¹  Ulf Reimer²  Pavlo Holenya²  Sergio Arpino³  Francesco Labonia³  Luigi Russo³  Ernesta Cavalcanti³  Maria Antonietta Isgrò³  Serena Meola³  Alberto Micillo⁴  Chiara Botti⁴  Andrea Cerasuolo⁵  Anna Lucia Tornesello⁵  Noemy Starita⁵  Maria Lina Tornesello⁵  Franco M. Buonaguro⁵  Luigi Atripaldi⁶  Silvia Sale⁶  Carmine Nicastro⁶ 

[1] Innovative Immunological Models, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Via Mariano Semmola, 80131, Naples, Italy;JPT Peptide Technologies GmbH, Berlin, Germany;Laboratory Medicine Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131, Naples, Italy;Laboratory of Clinical Pathology, Santobono-Pausilipon Children’s Hospital, 80129, Napoli, Italy;Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131, Naples, Italy;UOC Biochimica Chimica, AORN Ospedali dei Colli P.O. Monaldi, Naples, Italy;

关键词: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2);    COVID-19;    Peptide microarray;    Neutralizing antibodies;    Peptide biomarkers;    Children SARS-CoV-2 infection;   

DOI  :  10.1186/s12967-023-03963-5

 received in 2023-01-03, accepted in 2023-02-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients.MethodsWe included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5).ResultsAll patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels.ConclusionsOverall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.

【 授权许可】

CC BY   
© The Author(s) 2023

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