# Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants **Authors:** Javier García-Pérez, Alberto M. Borobia, Mayte Pérez-Olmeda, Antonio Portolés, Luis Castaño, Magdalena Campins-Artí, María Jesús Bertrán, Mercedes Bermejo, José Ramón Arribas, Andrea López, Ana Ascaso-del-Rio, Eunate Arana-Arri, Inmaculada Fuentes Camps, Anna Vilella, Almudena Cascajero, María Teresa García-Morales, María Castillo de la Osa, Carla Pérez Ingidua, David Lora, Paloma Jiménez-Santana, Silvia Pino-Rosa, Agustín Gómez de la Cámara, Erick De La Torre-Tarazona, Esther Calonge, Raquel Cruces, Cristóbal Belda-Iniesta, José Alcamí, Jesús Frías, Antonio J. Carcas, Francisco Díez-Fuertes, Lucía Díaz García, Lucía Díaz García, Elena Ramírez García, Enrique Seco Meseguer, Stefan Mark Stewart Balbàs, Alicia Marín Candón, Irene García García, Mikel Urroz Elizalde, Paula de la Rosa, Marta Sanz García, Cristina López Crespo, Vega Mauleón Martínez, Raquel de Madariaga Castell, Laura Vitón Vara, Rocío Prieto-Pérez, Emilio Vargas-Castrillón, Leonor Laredo, Ouhao Zhu-Huang, Teresa Iglesias, Natale Imaz-Ayo, Susana Meijide, Aitor García de Vicuña, Ana Santorcuato, Iraide Exposito, Sara de Benito, Alazne Bustinza, Mikel Gallego, Dolores García-Vázquez, Ana Belén de la Hoz, Gustavo Pérez-Nanclares, Josu Aurrekoetxea, Ines Urrutia, Rosa Martínez-Salazar, Janire Orcajo, Begoña Calvo, June Corcuera, Olaia Velasco, Anibal Aguayo, Xavier Martínez-Gómez, Susana Otero-Romero, Lluis Armadans, Blanca Borras-Bermejo, Oleguer Parés, Sonia Uriona, José Ángel Rodrigo Pendás, Cesar Llorente, José Santos, Laia Pinós, Lina Camacho, Judith Riera, Carla Sans, Antonia Agustí, Carmen Altadill, Carla Aguilar Blancafort, Gisela Gili Serrat, Aitana Plaza, Anna Feliu Prius, Maria Margarita Torrens, Esther Palacio, Gloria Torres, Julia Calonge, Elena Ballarin Alins, Eulàlia Pérez-Esquirol, Lourdes Vendrell Bosch, Marta Aldea, Eugènia Mellado, M Marcos, Marta Tortajada, Lourdes E. Barón-Mira, Laura Granés, Sulayman Lazaar, Sara Herranz, Montserrat Malet, Sebastiana Quesada, Anna Llupià, Victoria Olivé, Antoni Trilla, Begoña Gómez, Elisenda González, Sheila Romero, Francisco Javier Gámez, Cristina Casals, Laura Burunat, Juan José Castelló, Patricia Fernández, Josep Lluís Bedini, Jordi Vila, Juan Carlos Hurtado, Isabel Jado, Giovanni Fedele, Concepción Perea, Mónica González, Isabel Grajera, María Ángeles Murillo, Pilar Balfagón, Irene Díaz-Marín, Gema González-Pardo PMC · DOI: 10.1016/j.isci.2024.110728 · 2024-08-14 ## TL;DR A third dose of mRNA-1273 vaccine after ChAdOx1-S/BNT162b2 primes boosts antibody levels against SARS-CoV-2 variants more than a third BNT162b2 dose. ## Contribution Shows mRNA-1273 outperforms BNT162b2 as a third dose in neutralizing SARS-CoV-2 variants. ## Key findings - mRNA-1273 third dose induced higher neutralizing antibodies against Delta and BA.1 Omicron at day 28. - mRNA-1273 third dose showed higher neutralizing titers against G614 variant at day 90. - Suboptimal neutralization against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 variants was observed at day 180. ## Abstract CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739). •Higher NT50 titers was observed in mRNA-1273 arm against Delta and BA.1 at day 28•Higher NT50 titers was observed in mRNA-1273 arm against G614 variant at day 90•Suboptimal neutralization against recent Omicron variants was observed at day 180•Asymptomatic breakthrough infections do not ensure XBB.1.5 and JN.1 neutralization Higher NT50 titers was observed in mRNA-1273 arm against Delta and BA.1 at day 28 Higher NT50 titers was observed in mRNA-1273 arm against G614 variant at day 90 Suboptimal neutralization against recent Omicron variants was observed at day 180 Asymptomatic breakthrough infections do not ensure XBB.1.5 and JN.1 neutralization Immunology; Immune response ## Linked entities - **Diseases:** SARS-CoV-2 (MONDO:0100096) ## Full-text entities - **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049] ## Figures 5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11404211/full.md --- Source: https://tomesphere.com/paper/PMC11404211