Borobia, AlbertoCarcas, Antonio J.Pérez-Olmeda, MayteCastaño, LuisBertran, María JesúsGarcía-Pérez, JavierCampins, MagdalenaPortolés Pérez, AntonioGonzález-Pérez, MaríaGarcía Morales, Maria TeresaArana-Arri, EunateAldea, MartaDíez-Fuertes, FranciscoFuentes, InmaculadaAscaso del Río, AnaLora Pablos, DavidImaz-Ayo, NataleBarón-Mira, Lourdes E.Agustí, AntoniaPérez-Ingidua, CarlaGómez De La Cámara, Agustín RamónRamón Arribas, JoséOchando, JordiAlcamí. JoséBelda-Iniesta, CristóbalFrías, JesúsMartínez de Soto, LucíaRodríguez Mariblanca, AmeliaDíaz García, LucíaRamírez García, ElenaSeco Meseguer, EnriqueStewart Balbás, Stefan MarkMarín Candón, AliciaGarcía García, IreneUrroz Elizalde, MikelMonserrat Villatoro, JaimeDe la Rosa, PaulaSanz García, MartaLópez Crespo, CristinaMauleón Martínez, VegaDe Madariaga Castell, RaquelVitón Vara, LauraGarcía Rodríguez, JulioBuño, AntonioLópez Granados, EduardoCámara, CarmenRey Cuevas, EstherAyllon García, PilarJiménez González, MaríaHernández Rubio, VictoriaMoraga Alapont, PalomaSánchez, AmparoPrieto, RocíoLlorente Gómez, SilviaMiragall Roig, CristinaAparicio Marlasca, MarinaDe la Calle, FernandoArsuaga, MartaDuque, BlancaMeijide, SusanaGarcía de Vicuña, AitorSantorcuato, AnaExpósito, IraideDe Benito, SaraAndia, JosebaCastillo, CristinaIrurzun, EstherCamino, JesúsTemprano, MikelGoikoetxea, JosuneBustinza, AlazneLarrea, MaialenGallego, MikelGarcía-Vázquez, DoloresDe la Hoz, Ana BelénPérez-Nanclares, GustavoPérez-Guzmán, EstíbalizIdoyaga,EnekoLamela, AdrianaOteo, JesúsCastillo de la Osa, MaríaHernández Gutiérrez, LourdesAndrés Galván, María ElenaCalonge, EstherBermejo, MercedesDe la Torre-Tarazona, Erick HumbertoCascajero, AlmudenaFedele, GiovanniPerea, ConcepciónCervera, IsabelBodega-Mayor, IreneMontes-Casado, MaríaPortolés, PilarBaranda, JanaGranés, LauraLazaar, SulaymanHerranz, SaraMellado, María EugeniaTortajada, MartaMalet, MontserratQuesada, SebastianaVilella, AnnaLlupià, AnnaOlivé, VictoriaTrilla, AntoniGómez, BegoñaGonzález, ElisendaRomero, SheilaGámez, Francisco JavierCasals, CristinaBurunat, LauraCastelló, Juan JoséFernández, PatriciaBedini, Josep LluísVila, JordiAguilar, CarlaAltadill, CarmenArmadans, LluisBorras-Bermejo, BlancaCalonge, JuliaCamacho, LinaFeliu, AnnaGili, GiselaLlorente, CesarMartínez-Gómez, XavierSusana Otero-Romero, SusanaPalacio, EstherOleguer Parés, OleguerLaia Pinós, LaiaAitana Plaza, AitanaJudit Riera-Arnau, JuditRodrigo-Pendás, José ÁngelSans, CarlaSantos, JoséTorres, GloriaTorrens, MargaritaUriona, SoniaBallarin Alins, ElenaPérez Esquirol, EulàliaVendrell Bosch, LourdesLaredo Velasco, LeonorUribe López, DianaGonzález Rojano, EsperanzaSánchez-Craviotto, ManuelRivas Paterna, Ana BelénIglesias Hernán-Gómez, TeresaRodríguez Galán, NataliaGil Marín. José AntonioÁlvarez-Morales, VerónicaNavalpotro, Ana BelénJiménez-Santamaría, M DoloresCardós, M CarmenHermoso, ElenaGarcía-Arenillas, MarPérez Macías, NataliaDomingo Fernández, AlexandraLópez Picado, AmandaMario Quiñones, JorgeDeidda, NicolettaGarcía-Franco, AnaTorvisco, José María2025-01-232025-01-232021Borobia AM, Carcas AJ, Pérez-Olmeda M, Castaño L, Bertran MJ, García-Pérez J, Campins M, Portolés A, González-Pérez M, García Morales MT, Arana-Arri E, Aldea M, Díez-Fuertes F, Fuentes I, Ascaso A, Lora D, Imaz-Ayo N, Barón-Mira LE, Agustí A, Pérez-Ingidua C, Gómez de la Cámara A, Arribas JR, Ochando J, Alcamí J, Belda-Iniesta C, Frías J; CombiVacS Study Group. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet. 2021 Jul 10;398(10295):121-130. doi: 10.1016/S0140-6736(21)01420-3. Epub 2021 Jun 25. Erratum in: Lancet. 2021 Aug 14;398(10300):582. doi: 10.1016/S0140-6736(21)01805-5. PMID: 34181880; PMCID: PMC8233007.0140-673610.1016/s0140-6736(21)01420-3https://hdl.handle.net/20.500.14352/115843Background: To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods: We did a phase 2, open-label, randomised, controlled trial on adults aged 18-60 years, vaccinated with a single dose of ChAdOx1-S 8-12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing. Findings: Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 BAU/mL (7371·53-8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69-112·99) to 3684·87 BAU/mL (3429·87-3958·83). The interventional:control ratio was 77·69 (95% CI 59·57-101·32) for RBD protein and 36·41 (29·31-45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation: BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article1474-547Xhttps://doi.org/10.1016/S0140-6736(21)01420-3https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01420-3/fulltextopen access519.2:61004.661Clinical trialImmunization SecondaryImmunogenicityCoronavirus spike glycoproteinMedicinaInmunologíaEstadística32 Ciencias Médicas1209 Estadística