Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity
Abstract COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monoval...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01156-3 |
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| author | Laura A. Bruno Celeste Pueblas Castro Agostina Demaría Lineia Prado Clara G. Fascetto Cassero Lucas M. Saposnik Federico Páez Córdoba Juan Manuel Rodriguez Giulia Piccini Roberta Antonelli Giulia Lapini Nigel Temperton Sabrina A. Del Priore Andres C. Hernando Insua Ingrid G. Kaufmann Julio C. Vega Juan M. Flo Karina A. Pasquevich Lorena M. Coria Juliana Cassataro |
| author_facet | Laura A. Bruno Celeste Pueblas Castro Agostina Demaría Lineia Prado Clara G. Fascetto Cassero Lucas M. Saposnik Federico Páez Córdoba Juan Manuel Rodriguez Giulia Piccini Roberta Antonelli Giulia Lapini Nigel Temperton Sabrina A. Del Priore Andres C. Hernando Insua Ingrid G. Kaufmann Julio C. Vega Juan M. Flo Karina A. Pasquevich Lorena M. Coria Juliana Cassataro |
| author_sort | Laura A. Bruno |
| collection | DOAJ |
| description | Abstract COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4+ T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity. |
| format | Article |
| id | doaj-art-dc3476351d3f4b018119ffc616350da7 |
| institution | DOAJ |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-dc3476351d3f4b018119ffc616350da72025-08-20T03:16:29ZengNature Portfolionpj Vaccines2059-01052025-05-0110111010.1038/s41541-025-01156-3Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunityLaura A. Bruno0Celeste Pueblas Castro1Agostina Demaría2Lineia Prado3Clara G. Fascetto Cassero4Lucas M. Saposnik5Federico Páez Córdoba6Juan Manuel Rodriguez7Giulia Piccini8Roberta Antonelli9Giulia Lapini10Nigel Temperton11Sabrina A. Del Priore12Andres C. Hernando Insua13Ingrid G. Kaufmann14Julio C. Vega15Juan M. Flo16Karina A. Pasquevich17Lorena M. Coria18Juliana Cassataro19Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Laboratorio Pablo CassaráVisMederi SrlVisMederi SrlVisMederi SrlViral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham MaritimeLaboratorio Pablo CassaráFundación Pablo Cassará, Unidad de I+D de BiofármacosLaboratorio Pablo CassaráUnidad de I+DLaboratorio Pablo CassaráInstituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650)Abstract COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4+ T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity.https://doi.org/10.1038/s41541-025-01156-3 |
| spellingShingle | Laura A. Bruno Celeste Pueblas Castro Agostina Demaría Lineia Prado Clara G. Fascetto Cassero Lucas M. Saposnik Federico Páez Córdoba Juan Manuel Rodriguez Giulia Piccini Roberta Antonelli Giulia Lapini Nigel Temperton Sabrina A. Del Priore Andres C. Hernando Insua Ingrid G. Kaufmann Julio C. Vega Juan M. Flo Karina A. Pasquevich Lorena M. Coria Juliana Cassataro Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity npj Vaccines |
| title | Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity |
| title_full | Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity |
| title_fullStr | Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity |
| title_full_unstemmed | Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity |
| title_short | Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity |
| title_sort | development of bivalent rbd adapted covid 19 vaccines for broad sarbecovirus immunity |
| url | https://doi.org/10.1038/s41541-025-01156-3 |
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