Research gives detailed understanding of SARS-CoV-2 Omicron sublineage antibody escape

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The emergence of the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant shortly led to a rise in an infection charges globally, regardless of excessive ranges of safety towards SARS-CoV-2 by pure an infection and vaccination. A extremely mutated spike protein is chargeable for the variant’s excessive transmissibility and immune evasion capabilities.

Study: SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns. Image Credit: MarieGrecha / Shutterstock.com

Research: SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns. Picture Credit score: MarieGrecha / Shutterstock.com

Background

Though prolonged vaccine dosing intervals and booster doses towards the ancestral SARS-CoV-2 pressure present some degree of safety towards the Omicron variant, neutralizing antibody titers towards this variant are a lot decrease as in comparison with different variants. A number of therapeutic monoclonal antibodies additionally seem like ineffective towards Omicron infections.

Many of the research on the resistance of the Omicron variant to antibody-mediated neutralization are restricted to the preliminary BA.1 Omicron pressure. Nonetheless, a number of sublineages of Omicron have subsequently emerged and additional elevated an infection charges. Subsequently, it is very important decide the antibody escape properties of those Omicron subvariants for the event of efficient preventive and therapeutic interventions.

A brand new Cell Host and Microbe research reveals the antibody-mediated neutralization of each present and rising sublineages of Omicron together with BA.1, BA.2, BA.4, BA.1.1, BA.2.12.1, and BA.5 at each the monoclonal and polyclonal ranges.

Concerning the research

The present research concerned the gathering of serum samples from coronavirus illness 2019 (COVID-19)-convalescent people between April and Could 2020. Research [articipants were followed up for the analysis of long-term immunity to SARS-CoV-2, with additional serum samples collected after booster immunization between May and August 2021. Serum samples were also collected from vaccinated individuals after completing the initial immunization regimen, as well as after receiving booster doses.

BA.2.12.1, BA.4, and BA.5 pseudoviruses were produced using an expression plasmid followed by the production of monoclonal antibodies. Thereafter, pseudovirus neutralization assays were conducted, along with an analysis of antibody amino acid sequences.

The spike amino acid changes relative to the wild-type SARS-CoV-2 spike protein were visualized using cryo-electron microscopy. The frequency of variant distribution was also analyzed.

Study findings

The BA.1 spike protein contains 39 different amino acid residues as compared to the ancestral SARS-CoV-2 strain. Although other Omicron sublineages shared several mutations with BA.1, they also consisted of various unique mutations. Although the BA.1/BA.2 sublineages were responsible for the first Omicron wave, they were rapidly outcompeted by the BA.4 and BA.5 sublineages.

Serum neutralizing activity was observed for samples that were collected at a median of 48 days post-infection with the ancestral SARS-CoV-2 strain. However, neutralizing activity was detectable in 0-15% of samples for BA.1 and BA1.1, while the activity was 45-50% for BA.2, BA.2.12.1, and BA.4/ 5. Booster immunization led to neutralizing activity against all the Omicron sublineages.

Additionally, 43-73% of vaccinated individuals exhibited neutralizing activity against Omicron following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine. Notably, booster immunization led to increased activity against all the Omicron sublineages. The neutralizing activity against BA.4 and BA.5 was low as compared to that against BA.1.1, BA.1, and BA.2 among vaccinated individuals.

Out of the 158 monoclonal antibodies that were produced and tested, only 18%, 22%, 17%, 23%, and 18% remained active against BA.1, BA.2, BA.1.1, BA.2.12.1, and both BA.4 and BA.5, respectively.

Slight variations in amino acid sequences of the antibodies were found to impact Omicron resistance and neutralization. The newly identified Omicron sublineages were also found to be able to escape from most monoclonal antibodies that were in clinical use. Bebtelovimab, along with R200-1F9, R568-1G9, and R207-2F11 antibodies, exhibited neutralizing activity against all Omicron sublineages.

Conclusions

The current study demonstrates that Omicron sublineages are capable of escaping neutralization from both vaccination and previous infection and were resistant to many monoclonal antibodies. Taken together, genomic surveillance, along with sensitivity assessments, are important for monitoring the constant evolution of SARS-CoV-2 and determining appropriate therapeutic and prophylactic measures.

Journal reference:

  • Gruell, H., Vanshylla, K., Korenkov, M., et al. (2022). SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns. Cell Host and Microbe. doi:10.1016/j.chom.2022.07.002.
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