Přejít k obsahu
Merck

A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions.

Nature communications (2022-07-28)
Yang Liu, Xianwen Zhang, Jianying Liu, Hongjie Xia, Jing Zou, Antonio E Muruato, Sivakumar Periasamy, Chaitanya Kurhade, Jessica A Plante, Nathen E Bopp, Birte Kalveram, Alexander Bukreyev, Ping Ren, Tian Wang, Vineet D Menachery, Kenneth S Plante, Xuping Xie, Scott C Weaver, Pei-Yong Shi
ANOTACE

We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (∆3678). The ∆3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The ∆3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the ∆3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the ∆3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter ∆3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that ∆3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use.

MATERIÁLY
Číslo produktu
Značka
Popis produktu

Sigma-Aldrich
Anti-GAPDH antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Interferon-α A Protein, Recombinant human, Purified Recombinant Human Interferon Alpha A (Hu-IFN-alphaA & Hu-IFN-alpha2a).