3dbf89b6bc0e8f6720b48fbc2154b9c2 vaccines-12-00840.pdf d7a40f18c37a7e8e7f0516f0a3f0b23a2c8f5786 vaccines-12-00840.pdf 714ea87afa3c75ee8c0aa7de006e625c427bf0a92d622b5cfe8661ea273b0d55 vaccines-12-00840.pdf Title: Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results Subject: (1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate. Keywords: JN.1; XBB.1.16; adapted vaccine; SARS-CoV-2 vaccine; adjuvanted protein vaccine; booster vaccine; COVID-19 Author: María Jesús López Fernández, Silvia Narejos, Antoni Castro, José María Echave-Sustaeta, María José Forner, Eunate Arana-Arri, José Molto, Laia Bernad, Raúl Pérez-Caballero, Julia G. Prado, Dàlia Raïch-Regué, Rytis Boreika, Nuria Izquierdo-Useros, Benjamin Trinité, Julià Blanco, Joan Puig-Barberà and Silvina Natalini Martínez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Jul 26 07:43:24 2024 CEST ModDate: Fri Jul 26 08:54:45 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3556494 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UQZHSH+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 RCGKQW+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 GQYIFQ+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 YMUYWF+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 SDIDBK+VnURWPalladioL Type 1 Custom yes yes yes 32 0 OQIVQT+EURM10 Type 1 Builtin yes yes yes 62 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 85 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 88 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 91 0 PDTLUH+CMSY10 Type 1 Builtin yes yes yes 100 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 108 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 111 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 114 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 125 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 128 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 131 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 142 0 LMNLGA+PalatinoLinotype CID TrueType Identity-H yes yes yes 145 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 151 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 154 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 162 0 LMNLGA+PalatinoLinotype CID TrueType Identity-H yes yes yes 165 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 171 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 174 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 184 0 LMNLGA+PalatinoLinotype CID TrueType Identity-H yes yes yes 187 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 193 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 196 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 207 0 LMNLGA+PalatinoLinotype CID TrueType Identity-H yes yes yes 210 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 216 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 219 0 LMNLFP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 229 0 LMNLGA+PalatinoLinotype CID TrueType Identity-H yes yes yes 232 0 LMNLGB+PalatinoLinotype TrueType WinAnsi yes yes no 238 0 LMNLGD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 241 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-05-31 02:15:50 CEST RepresentationInformation: vaccines-12-00840.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-05-30 15:52:13 CEST Size: 3556494 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 474 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Participants Destination: subsection.2.2 Item: Title: Randomization and Treatment Allocation Destination: subsection.2.3 Item: Title: Sample Size Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Ethical Considerations Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Characteristics Destination: subsection.3.1 Item: Title: PHH-1V81 Immunogenicity against Omicron XBB.1.16 and Omicron XBB.1.5 Variants Destination: subsection.3.2 Item: Title: PHH-1V81 Immunogenicity against Omicron XBB.1.16 and Omicron XBB.1.5 Variants by Participant Subgroups Destination: subsection.3.3 Item: Title: PHH-1V81 Immunogenicity against Omicron JN.1 Variant Destination: subsection.3.4 Item: Title: PPH-1V81 Cellular Immunogenicity Destination: subsection.3.5 Item: Title: Safety and Tolerability Results Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results Author: María Jesús López Fernández, Silvia Narejos, Antoni Castro, José María Echave-Sustaeta, María José Forner, Eunate Arana-Arri, José Molto, Laia Bernad, Raúl Pérez-Caballero, Julia G. Prado, Dàlia Raïch-Regué, Rytis Boreika, Nuria Izquierdo-Useros, Benjamin Trinité, Julià Blanco, Joan Puig-Barberà and Silvina Natalini Martínez Subject: (1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate. 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