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- W4313279999 abstract "Abstract Serum titers of SARS-CoV-2 neutralizing antibodies (nAb) correlate well with protection from symptomatic COVID-19, but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are life-long after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We therefore sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated potent induction of high titer nAb in measles-immune mice and confirmed the significant incremental contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin-display of the SARS-CoV-2 spike glycoprotein, and vaccine resurfacing. In animals primed and boosted with a MeV vaccine encoding the ancestral SARS-CoV-2 spike, high titer nAb responses against ancestral virus strains were only weakly cross-reactive with the omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the omicron BA.1 spike, antibody titers to both ancestral and omicron strains were robustly elevated and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that antigen engineering can enable the development of potent measles-based SARS-CoV-2 vaccine candidates." @default.
- W4313279999 created "2023-01-06" @default.
- W4313279999 creator A5003255394 @default.
- W4313279999 creator A5004889712 @default.
- W4313279999 creator A5005063202 @default.
- W4313279999 creator A5012985685 @default.
- W4313279999 creator A5030138267 @default.
- W4313279999 creator A5030642496 @default.
- W4313279999 creator A5034939555 @default.
- W4313279999 creator A5044143965 @default.
- W4313279999 creator A5053211416 @default.
- W4313279999 creator A5061771806 @default.
- W4313279999 creator A5073352488 @default.
- W4313279999 creator A5084684701 @default.
- W4313279999 creator A5090210510 @default.
- W4313279999 date "2022-12-16" @default.
- W4313279999 modified "2023-10-18" @default.
- W4313279999 title "Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants" @default.
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