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Pre-existing anti-vector immunity to adenovirus-inspired VLP vaccines shows an adjuvant-dependent antagonism

Title: Pre-existing anti-vector immunity to adenovirus-inspired VLP vaccines shows an adjuvant-dependent antagonism
Authors: Gallet, Salomé; Hannani, Dalil; Dergan-Dylon, Sebastian; Vassal-Stermann, Emilie; Bally, Isabelle; Chevillard, Christopher; Fenel, Daphna; Epaulard, Olivier; Poignard, Pascal; Fender, Pascal
Contributors: Institut de biologie structurale (IBS - UMR 5075); Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA); Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC); VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP); Université Grenoble Alpes (UGA); the ANR Flash COVID program; ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010); ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Source: EISSN: 2076-393X ; Vaccines ; https://hal.science/hal-04970602 ; Vaccines, 2025, 13 (3), pp.238. ⟨10.3390/vaccines13030238⟩ ; https://www.mdpi.com/2076-393X/13/3/238
Publisher Information: CCSD; MDPI
Publication Year: 2025
Collection: Université Grenoble Alpes: HAL
Subject Terms: [SDV]Life Sciences [q-bio]
Description: International audience ; Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived from human-infecting viruses, preexisting immunity may influence the immune response they elicit, warranting further investigation. Methods: We have developed a 60-mer VLP derived from human adenovirus type 3, a common pathogen. We investigated the impact of pre-existing adenovirus immunity on the immunization outcome against the linear S14P5 epitope of SARS-CoV-2, which was engineered into the particle (Ad-VLP-S14P5). To this end, antibody responses to S14P5 were evaluated following immunization with Ad-VLP-S14P5 in either naive or vector-primed mice. Results: Mice with pre-existing anti-vector immunity exhibited significantly greater anti-S14P5 antibody responses compared to vector-naive animals, demonstrating a beneficial impact of prior anti-adenovirus responses. However, the addition of an oil-in-water adjuvant for the immunizations abolished this positive impact, even leading to a deleterious effect of the pre-existing anti-vector immunity. Conclusions: The data suggest that the immune status against immunizing VLPs must be taken into consideration when designing immunization protocols. Importantly, the effects of prior immunity may vary depending on the nature of the protocol, including factors such as adjuvant use.
Document Type: article in journal/newspaper
Language: English
DOI: 10.3390/vaccines13030238
Availability: https://hal.science/hal-04970602; https://hal.science/hal-04970602v1/document; https://hal.science/hal-04970602v1/file/Gallet%20et%20al.%20Vaccines.pdf; https://doi.org/10.3390/vaccines13030238
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.9C3B41FD
Database: BASE