2026-04-17T14:07:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/94912025-05-03T16:21:09Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial Garriga, Carme Prenafeta, Antoni Moros, Alexandra Cañete, Manuel Barreiro, Antonio Sans-Pola, Carla Otero-Romero, Susana Martínez-Gómez, Xavier Corominas Garcia, Júlia Institut Català de la Salut [Corominas J, Garriga C, Prenafeta A, Moros A, Cañete M, Barreiro A] HIPRA, Amer, Girona, Spain. [Otero Romero S] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat Docent, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosis Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Martinez Gomez X] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat Docent, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sans-Pola C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Recerca de Farmacologia Clínica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus COVID-19 (Malaltia) - Vacunació Immunoglobulines DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections Other subheadings::Other subheadings::Other subheadings::/prevention & control CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Viral CHEMICALS AND DRUGS::Complex Mixtures::Biological Products::Vaccines ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus Otros calificadores::Otros calificadores::Otros calificadores::/prevención & control COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos víricos COMPUESTOS QUÍMICOS Y DROGAS::mezclas complejas::productos biológicos::vacunas Neutralizing antibodies; Protein-based vaccine; SARS-CoV-2 Anticuerpos neutralizantes; Vacuna a base de proteínas; SARS-CoV-2 Anticossos neutralitzants; Vacuna a base de proteïnes; SARS-CoV-2 Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U. 2023-05-10T06:58:36Z 2023-05-10T06:58:36Z 2023-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Corominas J, Garriga C, Prenafeta A, Moros A, Cañete M, Barreiro A, et al. Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial. Lancet Reg Heal Eur. 2023 May;28:100613. 2666-7762 https://hdl.handle.net/11351/9491 10.1016/j.lanepe.2023.100613 37131861 eng The Lancet Regional Health - Europe;28 https://doi.org/10.1016/j.lanepe.2023.100613 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf Elsevier Scientia