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Murine antibody 4B1D3 exhibits broad cross-reactivity and neutralizing activity against SARS-CoV-2 variants

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Silva, Mariangela de Oliveira ; Daher, Isabela Pazotti ; Ibrahim, Catarina Harumi Oda ; de Souza, Edmarcia Elisa ; Postol, Edilberto ; Alencar, Raquel Elaine de ; Silva, Guilherme Antonio de Souza ; Marques, Rodolfo Ferreira ; Adami, Flavia Lopes ; Schuch, Viviane ; Yamamoto, Marcio Massao ; Almeida, Bianca da Silva ; Koike, Gabriela ; Azevedo, Isabela Resende ; Castro-Amarante, Maria Fernanda ; Rosa, Daniela Santoro ; Durigon, Edison Luiz ; Wrenger, Carsten ; Cunha-Neto, Edecio ; Kalil, Jorge ; Boscardin, Silvia Beatriz
Número total de Autores: 21
Tipo de documento: Artigo Científico
Fonte: VIROLOGY; v. 611, p. 10-pg., 2025-10-01.
Resumo

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019, spurred a global pandemic, prompting an unprecedented international mobilization in vaccination and public health strategies. Although the pandemic is now under greater control, the worldwide dissemination of variants of concern (VOCs) has led to resistance and decreased vaccine efficacy, highlighting the urgent need for broadspectrum therapeutic and preventive solutions. In this study, we employed hybridoma technology to generate monoclonal antibodies (mAbs) from mice immunized with the SARS-CoV-2 Wuhan Spike protein trimer. We selected clones producing anti-Spike receptor-binding domain (RBD) mAbs and characterized a panel of four mAbs to assess their potential as antiviral agents and their utility as tools in research and diagnostics. Our results showed that all mAbs recognized the SARS-CoV-2 Wuhan strain in infected cells through immunofluorescence assay. Moreover, the binding profiles of these mAbs against the RBD protein from various SARS-CoV-2 variants revealed distinct reactivity and loss of binding as VOCs emerged. However, one mAb, named 4B1D3, showed the most promising features, exhibiting broad binding and neutralizing capacity across all tested SARS-CoV-2 variants, including Omicron BA.2, BA.4/5 and XBB.1.5 sublineages. Furthermore, a single prophylactic dose of the 4B1D3 mAb provided protection to K18-hACE2 mice against a lethal challenge with SARS-CoV-2 Wuhan strain. In conclusion, these mAbs represent valuable tools for research and diagnostics and have significant potential for the development of new therapeutic strategies against SARS-CoV-2 variants. (AU)

Processo FAPESP: 14/50890-5 - INCT 2014: Investigação em Imunologia
Beneficiário:Jorge Elias Kalil Filho
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 18/07142-9 - Influência das Vias de Sinalização de STAT1, STAT3, STAT5 e STAT6 em Células Dendríticas Convencionais na Instrução da Resposta de Células T Auxiliares
Beneficiário:Silvia Beatriz Boscardin
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 21/14197-7 - Anticorpos neutralizantes para as diferentes variantes de preocupação do SARS-CoV-2 em indivíduos convalescentes e imunizados com diferentes vacinas contra a COVID-19
Beneficiário:Isabela Pazotti Daher
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 21/11971-3 - Anticorpos monoclonais quiméricos como estratégia de ativação de respostas imunológicas contra infecção pelo SARS-CoV 2
Beneficiário:Mariângela de Oliveira Silva
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado