biostudies-literatureChang SNational Research Foundation of Korea (NRF)Korea Research Institute of Bioscience and Biotechnology (KRIBB)Korea Health Industry Development InstituteNational Research Foundation of KoreaKorea Health Industry Development Institute (KHIDI)Korea Research Institute of Bioscience and Biotechnologye2313681121https://www.ebi.ac.uk/biostudies/studies/S-EPMC10927586biostudies-literatureUnknown121(10)The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of AmericaStrategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.PMC10927586HV23C0018KGM45723232022M3A9J1072296Park HKim JOVolz EKim GSeo HHong JJShin JBae SEChang SPark SJung IKBaek SHKang CYShin KSKim JHPark BfalseStrategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.2024-01-01T00:00:00Z2024 Mar2025-04-26T14:19:21.179Z2025-04-06T14:31:15.565ZS-EPMC109275863840823810.1073/pnas.2313681121