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oai:recercat.cat:10256/254702024-10-29T16:14:25Zcom_2072_452955com_2072_2054col_2072_452960

2024-10-29T16:14:25Z urn:hdl:10256/25470 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 Corominas Garcia, Júlia Garriga, Carme Prenafeta i Amargós, Antoni Moros, Alexandra Cañete, Manuel Barreiro, Antonio González-González, Luis Madrenas, Laia Güell, Irina Clotet, Bonaventura Izquierdo-Useros, Nuria Raïch-Regué, Dàlia Gallemí, Marçal Blanco, Julià Pradenas, Edwards Trinitè, Benjamin Prado, Julia G. Blanch-Lombarte, Oscar Pérez-Caballero, Raúl Plana, Montserrat Esteban, Ignasi Pastor-Quiñones, Carmen Núñez-Costa, Xavier Abu Taleb, Rachel McSkimming, Paula Soriano, Alex Nava, Jocelyn Anagua, Jesse Omar Ramos Blanes, Rafel Martí Lluch, Ruth Corpes Comes, Aida Otero Romero, Susana Martínez Gómez, Xavier Sans-Pola, Carla Moltó, José Benet, Susana Bailón, Lucía Arribas, Jose R. Borobia, Alberto M. Queiruga Parada, Javier Navarro-Pérez, Jorge Forner Giner, Maria José Ortí Lucas, Rafael Vázquez Jiménez, María del Mar Oña Compán, Salvador Alvarez-Mon, Melchor Troncoso, Daniel Arana-Arri, Eunate Meijide, Susana Imaz-Ayo, Natale Muñoz García, Patricia Villa Martínez, Sofía de la Rodríguez Fernández, Sara Prat, Teresa Torroella, Èlia Ferrer Soler, Laura Medicaments -- Desenvolupament Drug development Medicaments -- Assaigs clínics Drugs -- Testing COVID-19 (Malaltia) COVID-19 (Disease) Vacunes Vaccines 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 2024-10-29T16:14:25Z 2024-10-29T16:14:25Z 2023-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed http://hdl.handle.net/10256/25470 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lanepe.2023.100613 info:eu-repo/semantics/altIdentifier/eissn/2666-7762 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier The Lancet Regional Health Europe, 2023, vol. 28, art. núm. 100613 Articles publicats (D-CM)