Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines

Journal of Virology
Vineet D MenacheryRalph S Baric

Abstract

With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated...Continue Reading

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Citations

Jul 26, 2019·Journal of Virology·Kevin W GraepelMark R Denison
Sep 16, 2020·Human Vaccines & Immunotherapeutics·Rajat MudgalShailly Tomar
Jan 20, 2019·Viruses·Craig Schindewolf, Vineet D Menachery
Apr 17, 2020·Vaccines·Sergio Rosales-MendozaJaime I Arévalo-Villalobos
Dec 31, 2020·Vaccines·Shilu MathewHadi M Yassine
Nov 18, 2020·3 Biotech·N S Sampath KumarMahesh Kumar
Jan 31, 2021·Nature Protocols·Xuping XiePei-Yong Shi
Jan 12, 2021·Frontiers in Immunology·Jing ZhaoQiwei Zhang
Dec 21, 2020·Journal of Biomedical Science·Yen-Der LiT-C Wu
Sep 10, 2020·Asian Journal of Pharmaceutical Sciences·Lanxiang HuangFubing Wang
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rambod AbiriSonia Malik
Aug 7, 2021·Vaccines·Srividhya VenkataramanMounir Abouhaidar

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