The study investigates antibody avoidance patterns in the SARS-CoV-2 omicron substrain

Recent studies posted on bioRxiv* The preprint server outlined the antibody evasion ability of the common severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron substrain.

Background

Treatment and protection of coronavirus disease 2019 (COVID-19) is based on antibodies that neutralize SARS-CoV-2. As a result, SARS-CoV-2 mutants that exhibit antibody avoidance endanger important prophylactic and therapeutic approaches to COVID-19.

Neutralization susceptibility of the SARS-CoV-2 Omicron BA.1 subline after COVID-19 or its vaccination is due to the significant number of mutations in the peaplomer (S) protein of the Variant of Concern (VOC). , Not enough. Therefore, Omicron infection leads to lower vaccine efficacy and better reinfection rates than other SARS-CoV-2 mutants.

In particular, the newly emerging subline of Omicron, BA.2 and BA.1.1, has rapidly become the mainstream circulating SARS-CoV-2 mutant.

About research

In this study, scientists determined polyclonal serum activity against SARS-CoV-2 Omicron BA.2, BA.1, and BA.1.1 substrains in 50 COVID-19 vaccinated or convalescent individuals. .. The authors also described the antibody susceptibility of the SARS-CoV-2 mutant at the monoclonal level using 163 antibodies.

All research volunteers submitted written informed consent prior to registration. A total of 20 serum samples from patients recovered with COVID-19 were sourced from the University of Cologne Hospital between April and May 2020.

People with a history of COVID-19 confirmed by polymerase chain reaction (PCR) were enrolled in this study within 8 weeks of the diagnosis or onset of symptoms of SARS-CoV-2 to assess long-term immunity to the virus. Was tracked for a long time. The individual was probably infected with a strain such as the ancestral SARS-CoV-2Wu01.

In addition, 30 serum samples were collected from healthcare workers vaccinated with SARS-CoV-2. Health care workers vaccinated with COVID-19 at Charité – Universitätsmedizin in Berlin, Germany, were included in this study regardless of their health status.

All serum samples were screened for antibodies to the SARS-CoV-2 nucleocapsid (N) protein using the SeraSpot immunoassay based on the anti-SARS-CoV-2 immunoglobulin G (IgG) microarray.

The vaccination cohort did not include samples from people who were previously infected with SARS-CoV-2 and were positive for SARS-CoV-2. Nucleic acid Amplification test, or detectable anti-N antibody. In addition, both the infected and vaccinated groups received the COVID-19 messenger ribonucleic acid (mRNA) BNT162b2 vaccine twice, with a median of 9 and 14 months after SARS-CoV-2 infection, respectively. I was vaccinated.

Serum samples were procured after centrifugation and stored at -80 ° C until analysis. The ability of serum samples to neutralize the three Omicron substrains was analyzed using a lentivirus base. Pseudo virus experiment. The ancestral SARS-CoV-2Wu01 strain was used as a reference.

Results and discussion

The study results show that individuals who recovered with SARS-CoV-2 had a median age of 51 years and experienced asymptomatic or mild COVID-19. All serum samples procured from the COVID-19 convalescent phase after a median of 48 days showed 100% neutralization of the SARS-CoV-2 Wu01 strain. On the contrary, serum activity against the three Omicron substrains was substantially lower at 50%, 0%, and 15% for the BA.2, BA.1.1, and BA.1 substrains, respectively. Nonetheless, COVID-19 booster vaccination with a median of 33 days in all SARS-CoV-2 recovery patients increased the neutralizing activity of Omicron.

In the vaccination cohort, the ability to neutralize the Wu01 and Omicron substrains was detected in all 30 subjects and 43-73%, respectively, at a median of 28 days after the second vaccination. In addition, at a median of 29 days after booster immunization, the sample showed an 8-fold increased serological activity against the Wu01 strain and a significantly increased neutralizing activity against Omicron.

Especially most Wu01-Neutralizing antibody Lost activity against the Omicron substrain. Most BA.1 neutralizing antibodies such as R568-1G9 and R207-2F11 were also active against BA.2 and BA.1.1, but antibodies with BA.2-specific omicron neutralizing activity. The subgroup of means the difference in antigenicity of the substrain.

Furthermore, the high incidence of BA.2 neutralizing and BA.1 neutralizing antibodies among the analyzed antibodies indicates that the resistance-related properties of the BA.2S protein are low.

The majority of the 18 evaluated monoclonal antibodies (mAbs) under development or clinical use neutralized the SARS-COV-2Wu01 strain. However, sotrovimab was not very effective against Wu01. On the other hand, most mAbs in clinical use or development were resistant to the common Omicron BA.2, BA.1.1, and BA.1 substrains. However, the susceptibility of Omicron to these antibodies can vary significantly at the substrain level.

For example, DZIF-10c mAb neutralized the Omicron BA.1 substrain but was inactive against the BA.1.1 substrain. Silgabimab showed significant neutralization activity against BA.2, comparable to Wu01 neutralization levels, and was more than 800-fold better than BA.1.1 and BA.1. Of all the mAbs analyzed, bebutellobimab showed a strong neutralizing ability against the three Omicron substrains. Therefore, substrain identification or epidemiology should be considered when selecting mAbs for the treatment or prevention of Omicron infections.

Conclusion

The results of the study revealed a significant but similar reduction in serological immunity to the three Omicron substrains of SARS-CoV-2 vaccinated or virus-infected individuals. This was especially elevated after COVID-19 booster vaccination. Nonetheless, significant variations in susceptibility to different antibodies by the Omicron BA.2 and BA.1 substrains reveal their unique escape patterns that affect the clinical use of antibodies. Current research results have important implications for the SARS-CoV-2 vaccination approach and the antibodies used in the treatment and prevention of COVID-19.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.