Journal article
SARS-CoV-2-derived RNA replicons as safe and effective vaccines
Proceedings of the National Academy of Sciences - PNAS, Vol.122(39), e2516587122
09/30/2025
DOI: 10.1073/pnas.2516587122
PMCID: PMC12501190
PMID: 40991433
Abstract
A collection of RNA replicons (RRs) derived from severe acute respiratory syndrome 2 (SARS-CoV-2) for use in vaccine design was constructed by genetic engineering using bacterial artificial chromosomes. A replicon, which was deleted in six genes (3a, 3c, E, 6, 7a, and 7b) was selected. Cells infected with the RR vaccine candidate led to the formation of virus-like particles that, due to the failure of being secreted, increase vaccine safety, in contrast to the wild type virions. The replicon maintained the production of RNAs encoding at least proteins S, M, and N for several days. Intranasal immunization with the RR of transgenic mice, expressing human ACE2, elicited respiratory mucosal immunity. Immunization protected against challenge with SARS-CoV-2, inducing IgG, IgM, and IgA antibodies to the spike (S) protein, the receptor binding domain, N and M proteins, and cellular immune responses (CD4
, CD8
, and long-term memory T cells). Coinfection of cells with the RR vaccine and a full-length SARS-CoV-2 led to a significant inhibition of replication of full-length virus, increasing the safety of the RR vaccine. The RR vaccine induced a minor inflammatory reaction in the absence of major side effects and was stable at different temperatures. An updated RR expressing XBB.1.5 S protein elicited neutralizing antibodies against the homologous virus and provided full protection against recent SARS-CoV-2 variants.
Details
- Title: Subtitle
- SARS-CoV-2-derived RNA replicons as safe and effective vaccines
- Creators
- Marta Villarejo-Torres - Universidad Autónoma de MadridIván Nombela-Diaz - Universidad Autónoma de MadridDiego Muñóz-Santos - Universidad Autónoma de MadridMercedes Ruiz-Yuste - Universidad Autónoma de MadridAna Marchena-Pasero - Universidad Autónoma de MadridMaría A Rueda-Huélamo - Universidad Autónoma de MadridJorge Ripoll-Gómez - Universidad Autónoma de MadridPedro J Sánchez-Cordón - Instituto Nacional de Investigación y Tecnología Agraria y AlimentariaLaura Fernandez Del Ama - CIUDADJosé M Honrubia - Universidad Autónoma de MadridJavier Gutiérrez-Álvarez - Universidad Autónoma de MadridJesús Hurtado-Tamayo - Universidad Autónoma de MadridRicardo Requena-Platek - Universidad Autónoma de MadridMaría Guzmán - Universidad Autónoma de MadridJose M Casasnovas - Universidad Autónoma de MadridJuan F García-Arriaza - Universidad Autónoma de MadridPatricia Perez - Universidad Autónoma de MadridBeatriz Martin-Jouve - Universidad Autónoma de MadridTania Matamoros - Centro de Biología Molecular Severo OchoaBelén Pintado - TransgeneStanley Perlman - University of IowaIsabel Sola - Universidad Autónoma de MadridSonia Zuñiga - Universidad Autónoma de MadridLuis Enjuanes - Universidad Autónoma de Madrid
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.122(39), e2516587122
- DOI
- 10.1073/pnas.2516587122
- PMID
- 40991433
- PMCID
- PMC12501190
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 1091-6490
- eISSN
- 1091-6490
- Publisher
- NATL ACAD SCIENCES
- Grant note
- PIPF-2022/SAL-GL-24549 / Comunidad de Madrid (Community of Madrid) FPU21/02704 / Government of Spain PREP2022-0005777 / Government of Spain ISOLDA Project No. 848166-2 / European Commission (EC) PID2022-140328OB-I00 / Government of Spain P01 AI060699 / NIAID NIH HHS PID2019-107001RB-I00UE / Government of Spain PID2019-107001RB-I00 / Government of Spain Y2020/BIO- 6576 / Comunidad de Madrid (Community of Madrid)
- Language
- English
- Date published
- 09/30/2025
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984966333902771
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