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Background <p>The continuous emergence of SARS-CoV-2 variants and subvariants poses significant public health challenges. The latest designated subvariant JN.1, with all its descendants, shows more than 30 mutations in the spike gene. JN.1 has raised concerns due to its genomic diversity and its potential to enhance transmissibility and immune evasion. This study aims to analyse the molecular characteristics of JN.1-related lineages (JN.1*) identified in Italy from October 2023 to April 2024 and to evaluate the neutralization activity against JN.1 of a subsample of sera from individuals vaccinated with XBB.1.5 mRNA.</p> Methods <p>The genomic diversity of the spike gene of 794 JN.1* strain was evaluated and phylogenetic analysis was conducted to compare the distance to XBB.1.5. Moreover, serum neutralization assays were performed on a subsample of 19 healthcare workers (HCWs) vaccinated with the monovalent XBB.1.5 mRNA booster to assess neutralizing capacity against JN.1.</p> Results <p>Sequence analysis displayed high spike variability between JN.1* and phylogenetic investigation confirmed a substantial differentiation between JN.1* and XBB.1.5 spike regions with 29 shared mutations, of which 17 were located within the RBD region. Pre-booster neutralization activity against JN.1 was observed in 42% of HCWs sera, increasing significantly post-booster, with all HCWs showing neutralization capacity three months after vaccination. A significant correlation was found between anti-trimeric Spike IgG levels and neutralizing titers against JN.1.</p> Conclusions <p>The study highlights the variability of JN.1* in Italy. Results on a subsample of sera from HCWs vaccinated with XBB.1.5 mRNA booster vaccine suggested enhanced neutralization activity against JN.1.</p>

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JN.1 variants circulating in Italy from October 2023 to April 2024: genetic diversity and immune recognition

  • 期刊论文

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  • 发表日期：

    2025年2月28日

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  • Emanuela Giombini,
  • Ilaria Schiavoni,
  • Luigina Ambrosio,
  • Alessandra Lo Presti,
  • Angela Di Martino,
  • Stefano Fiore,
  • Pasqualina Leone,
  • Francesca Fortunato,
  • Rosa Prato,
  • Giorgio Fedele,
  • Anna Teresa Palamara,
  • Paola Stefanelli,
  • Liborio Stuppia,
  • Federico Anaclerio,
  • Giovanni Savini,
  • Cesare Cammà,
  • Luigi Possenti,
  • Domenico Dell’Edera,
  • Antonio Picerno,
  • Teresa Lopizzo,
  • Maria Teresa Fiorillo,
  • Rosaria Oteri,
  • Giuseppe Viglietto,
  • Pasquale Minchella,
  • Francesca Greco,
  • Antonio Limone,
  • Giovanna Fusco,
  • Claudia Tiberio,
  • Luigi Atripaldi,
  • Mariagrazia Coppola,
  • Davide Cacchiarelli,
  • Antonio Grimaldi,
  • Stefano Pongolini,
  • Erika Scaltriti,
  • Vittorio Sambri,
  • Giorgio Dirani,
  • Silvia Zannoli,
  • Tiziana Lazzarotto,
  • Giada Rossini,
  • Federica Baldan,
  • Sabrina Lombino,
  • Pierlanfranco D’Agaro,
  • Ludovica Segat,
  • Fabio Barbone,
  • Raffaella Koncan,
  • Antonio Battisti,
  • Patricia Alba,
  • Maria Teresa Scicluna,
  • Silvia Angeletti,
  • Elisabetta Riva,
  • Fulvia Pimpinelli,
  • Maurizio Fanciulli,
  • Alice Massacci,
  • Maurizio Sanguinetti,
  • Fabrizio Maggi,
  • Martina Rueca,
  • Cesare Ernesto Maria Gruber,
  • Ombretta Turriziani,
  • Carlo Federico Perno,
  • Francesca Ceccherini-Silberstein,
  • Maria Concetta Bellocchi,
  • Bianca Bruzzone,
  • Giancarlo Icardi,
  • Andrea Orsi,
  • Rea Valaperta,
  • Maria Oggionni,
  • Sophie Testa,
  • Fabio Sagradi,
  • Arnaldo Caruso,
  • Serena Messali,
  • Diana Fanti,
  • Alice Nava,
  • Sergio Malandrin,
  • Annalisa Cavallero,
  • Claudio Francesco Farina,
  • Marco Arosio,
  • Ferruccio Ceriotti,
  • Sara Colonia Uceda Renteria,
  • Stefania Paganini,
  • Anna Maria Di Blasio,
  • Erminio Torresani,
  • Maria Beatrice Boniotti,
  • Cristina Bertasio,
  • Nicola Clementi,
  • Michela Sampaolo,
  • Federica Novazzi,
  • Nicasio Mancini,
  • Maria Rita Gismondo,
  • Valeria Micheli,
  • Fausto Baldanti,
  • Federica AM Giardina,
  • Antonio Piralla,
  • Federica Zavaglio,
  • Francesca Rovida,
  • Elena Pariani,
  • Cristina Galli,
  • Laura Pellegrinelli,
  • Stefano Menzo,
  • Massimiliano Scutellà,
  • Valentina Felice,
  • Elisabetta Pagani,
  • Irene Bianconi,
  • Angela Maria Di Pierro,
  • Lucia Collini,
  • Giovanni Lorenzin,
  • Valeria Ghisetti,
  • Sara Gilardi,
  • Alice Bartolini,
  • Daniela Cantarella,
  • Simone Peletto,
  • Giuseppe Ru,
  • Pier Luigi Acutis,
  • Elena Bozzetta,
  • Maria Chironna,
  • Daniela Loconsole,
  • Antonio Parisi,
  • Fabio Arena,
  • Rossella De Nittis,
  • Giuseppina Iannelli,
  • Florigio Romano Lista,
  • Ferdinando Coghe,
  • Sergio Uzzau,
  • Salvatore Rubino,
  • Flavia Angioj,
  • Gabriele Ibba,
  • Caterina Serra,
  • Giovanna Piras,
  • Giuseppe Mameli,
  • Rosanna Asproni,
  • Francesca Di Gaudio,
  • Stefano Vullo,
  • Stefano Reale,
  • Teresa Pollicino,
  • Francesco Vitale,
  • Fabio Tramuto,
  • Stefania Stefani,
  • Guido Scalia,
  • Concetta Ilenia Palermo,
  • Giuseppe Mancuso,
  • Vincenzo Bramanti,
  • Carmelo Fidone,
  • Giuseppe Barrano,
  • Mauro Pistello,
  • Gian Maria Rossolini,
  • Francesca Malentacchi,
  • Maria Grazia Cusi,
  • Antonella Mencacci,
  • Barbara Camilloni,
  • Calogero Terregino,
  • Alice Fusaro,
  • Isabella Monne,
  • Edoardo Giussani,
  • Davide Gibellini,
  • Emil Tonon,
  • Riccardo Cecchetto,
  • Laura Squarzon,
  • Mosè Favarato,
  • Valeria Biscaro,
  • Elisa Vian,
  • Silvia Ragolia,
  • Michela Pascarella,
  • Fabio Buffoli,
  • Isabella Cerbaro

摘要

Background

The continuous emergence of SARS-CoV-2 variants and subvariants poses significant public health challenges. The latest designated subvariant JN.1, with all its descendants, shows more than 30 mutations in the spike gene. JN.1 has raised concerns due to its genomic diversity and its potential to enhance transmissibility and immune evasion. This study aims to analyse the molecular characteristics of JN.1-related lineages (JN.1*) identified in Italy from October 2023 to April 2024 and to evaluate the neutralization activity against JN.1 of a subsample of sera from individuals vaccinated with XBB.1.5 mRNA.

Methods

The genomic diversity of the spike gene of 794 JN.1* strain was evaluated and phylogenetic analysis was conducted to compare the distance to XBB.1.5. Moreover, serum neutralization assays were performed on a subsample of 19 healthcare workers (HCWs) vaccinated with the monovalent XBB.1.5 mRNA booster to assess neutralizing capacity against JN.1.

Results

Sequence analysis displayed high spike variability between JN.1* and phylogenetic investigation confirmed a substantial differentiation between JN.1* and XBB.1.5 spike regions with 29 shared mutations, of which 17 were located within the RBD region. Pre-booster neutralization activity against JN.1 was observed in 42% of HCWs sera, increasing significantly post-booster, with all HCWs showing neutralization capacity three months after vaccination. A significant correlation was found between anti-trimeric Spike IgG levels and neutralizing titers against JN.1.

Conclusions

The study highlights the variability of JN.1* in Italy. Results on a subsample of sera from HCWs vaccinated with XBB.1.5 mRNA booster vaccine suggested enhanced neutralization activity against JN.1.