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Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal… — Europe PMC PMID:38739647

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/38739647
DOI: 10.1371/journal.ppat.1012198
License (as archived): CC0-1.0
Archived: 2026-10-06T18:31:18.694Z
SHA-256 of the archived text: 815967695d042f608041e2bd08229173f6bbe652437a56fb2c759ec684abb2e4
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How to cite

Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal… — Europe PMC PMID:38739647 — Europe PMC (en), https://europepmc.org/article/MED/38739647 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_47bbccef09ca (Metraipolis archive dc_47bbccef09ca, sha256 815967695d042f608041e2bd08229173f6bbe652437a56fb2c759ec684abb2e4)

BibTeX

@misc{dc47bbccef09ca,
  title = {Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal… — Europe PMC PMID:38739647},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/38739647},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_47bbccef09ca; sha256 815967695d042f608041e2bd08229173f6bbe652437a56fb2c759ec684abb2e4},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/38739647. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PLoS pathogens, 2024 (prima pubblicazione 2024-05-13).
Identificativi: PMID 38739647 · PMCID PMC11115275 · DOI 10.1371/journal.ppat.1012198.
Descrittori MeSH principali: Respiratory Syncytial Virus Infections; Vaccines, Attenuated; Respiratory Syncytial Virus Vaccines; Virus Replication; Open Reading Frames.
Pagina: https://europepmc.org/article/MED/38739647 — https://doi.org/10.1371/journal.ppat.1012198. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
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