The omicron variant of SARS-CoV-2 is more easily transmissible than many previous variants, and thus, spreads quite rapidly. This variant shows extensive mutations compared with earlier variants, but it is not well understood how they influence, e.g., the transmissibility and the effects of existing vaccines against omicron. However, the levels of laboratory safety required to study SARS-CoV-2 can slow down research.
Melanie Ott, Gladstone Institutes, Chan Zuckerberg Biohub, and University of California, all San Francisco, CA, USA, Jennifer A. Doudna, Gladstone Institutes, University of California, Berkeley, and Lawrence Berkeley National Laboratory, CA, USA, and colleagues have used SARS-CoV-2 virus-like particles (VLPs) with all four structural proteins of the virus to study the effects of the mutations in the omicron variant. They investigated the infectivity and the response to existing vaccines and therapeutic antibodies.
Infectivity
The virus-like particles were prepared using cell cultures that express the necessary proteins. Their infectivity was then tested using “receiver” cells that express ACE2 and TMPRSS2 receptors, which are important for cell entry.
The team found that VLPs simulating the omicron and delta variants showed higher assembly and cell entry than the “original” virus. These “improvements” were due to mutations in the S (spike) and N (nucleocapsid) proteins. Mutations in the membrane (M) and envelope (E) protein reduced particle assembly and might reduce viral fitness.
Vaccines
The researchers tested the neutralizing activity of antisera samples from different vaccinated or convalescent subjects against the VLPs.
They found that sera from doubly vaccinated or convalescent subjects were up to 15-fold less effective against omicron compared with the original virus strain. However, a recent third dose of an mRNA vaccine substantially improved the neutralization of omicron.
Antibodies
When the team tested whether available monoclonal antibodies can neutralize the VLPs, they found that the mutations in the omicron variant cause some commercially available antibodies to be completely ineffective. The comparatively new bebtelovimab showed robust neutralization for all studied variants and, according to the researchers, might be useful for treating patients infected with the omicron variant.
Overall, the team’s SARS-CoV-2 VLPs allow fast and comprehensive investigations of the effects of structural protein variants on infectivity and antibody neutralization.
- Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles,
Abdullah M. Syed, Alison Ciling, Taha Y. Taha, Irene P. Chen, Mir M. Khalid, Bharath Sreekumar, Pei-Yi Chen, G. Renuka Kumar, Rahul Suryawanshi, Ines Silva, Bilal Milbes, Noah Kojima, Victoria Hess, Maria Shacreaw, Lauren Lopez, Matthew Brobeck, Fred Turner, Lee Spraggon, Takako Tabata, Melanie Ott, Jennifer A. Doudna,
Proc. Natl. Acad. Sci. USA 2022.
https://doi.org/10.1073/pnas.2200592119
Also of Interest
- Collection: SARS-CoV-2 Virus
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