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ORIGINAL RESEARCH article

Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1414331
This article is part of the Research Topic Emerging SARS-COV-2 Variants: Genomic Variations, Transmission, Pathogenesis, Clinical Impact and Interventions, Volume III View all 25 articles

SARS-CoV-2 Infectivity and Antigenic Evasion: Spotlight on Isolated Omicron Sublineages

Provisionally accepted
Aldo Barrera Aldo Barrera 1Constanza Martinez-Valdebenito Constanza Martinez-Valdebenito 1Jenniffer Angulo Jenniffer Angulo 1Carlos Palma Carlos Palma 2Juan Hormazabal Juan Hormazabal 3Cecilia Vial Cecilia Vial 3Ximena Aguilera Ximena Aguilera 4Pablo Castillo-Torres Pablo Castillo-Torres 5Catalina Pardo Roa Catalina Pardo Roa 5María E. Balcells María E. Balcells 6Bruno Nervi Bruno Nervi 7Nicole Le Corre Nicole Le Corre 1,2Marcela Ferres Marcela Ferres 1,2*
  • 1 Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Santiago Metropolitan Region (RM), Chile
  • 2 Laboratorio de Infectología y Virología Molecular, Facultad de Medicina y Red de Salud UC CHRISTUS, Santiago, Chile
  • 3 Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile
  • 4 Centro de Epidemiología y Políticas de Salud, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile
  • 5 Departamento de Salud del Niño y el Adolescente, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 6 Departamento de Enfermedades Infecciosas del Adulto. Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 7 Departamento de Hematología y Oncología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

The final, formatted version of the article will be published soon.

    Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and evasion of immunity. This fact raises the question of whether natural or vaccine-acquired immunity will be sufficient to protect the population from future waves of SARS-CoV-2. Variants of concern like Delta and Omicron have been highlighted by their predominant circulation and reduced antibody neutralization. By the first trimester of 2023 in Chile as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Also, few studies using isolates from recent Omicron sub-lineages have been conducted, indicating a need for further investigation of their characteristics and implications. In this study, we analyze the characteristics of isolated SARS-CoV-2 from clinical samples, as for the ancestral B.1.1, Delta, Omicron BA.1 and sub-lineages of BA.2 and BA.5, assessing their infectivity in cell lines and their ability to evade neutralization. On cell culture, we observed dissimilar viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 with each variant, suggesting a decrease in the cytopathic effect compared to the ancestral B.1.1 strain. BA.2-derived sub-variants like XBB.1.5 showed attenuated viral replication, but BA.5-derived variants like BQ.1.1 resemble the replication rates of the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a reduction in neutralization against the BA.1, as for the following Omicron sub-lineages, showing a discrete but constant decrease in neutralization. Interestingly, BQ.1.1 showed a 6.1-fold more escape to neutralization than XBB.1.5, despite being less prevalent. Neutralization patterns were similar when tested sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules; however, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP. Our analysis provides important evidence regarding the balance between infectivity and antigenic escape that drives SARS-CoV-2 second-generation evolution in the population.

    Keywords: SARS-CoV-2, COVID-19, variants, omicron, isolated viruses

    Received: 08 Apr 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Barrera, Martinez-Valdebenito, Angulo, Palma, Hormazabal, Vial, Aguilera, Castillo-Torres, Pardo Roa, Balcells, Nervi, Le Corre and Ferres. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marcela Ferres, Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Santiago Metropolitan Region (RM), Chile

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.