In a recent study published on the bioRxiv* preprint server, researchers evaluate the sensitivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineage Omicron BA.2.75 to neutralization.
Study: Neutralization sensitivity of the SARS-CoV-2 Omicron BA.2.75 subline. Image credit: gan chaonan / Shutterstock.com
background
On July 15, 2022, the European Center for Disease Prevention and Control (ECDC) categorized SARS-CoV-2 sublineage Omicron BA.2.75 as a variant of interest (VOI). Genetic surveillance of BA.2.75 indicated that this variant was responsible for a rapid increase in the number of sequenced infections.
Compared to the Omicron BA.2 sublineage, the BA.2.75 spike protein differed by nine amino acid residues in the N-terminal domain and the receptor-binding domain (RBD). These mutations have resulted in a significant reduction in viral susceptibility to neutralization by antibodies.
About the study
In the present study, researchers examine the effect of SARS-CoV-2 spike mutations on the activity of monoclonal and polyclonal antibodies by assessing the neutralization sensitivity of SARS-CoV-2 Omicron BA. 2.75.
Here, researchers collected serum samples from two longitudinal cohorts of healthcare workers (HCW) and the elderly who were eligible for the Pfizer-BioNTech BNT162b2 COVID-19 vaccination.
All collected serum samples were tested for the absence of antibodies directed against the SARS-CoV-2 nucleocapsid (N) protein, as this would suggest a history of previous SARS-CoV-2 infection. Participants who had a previous SARS-CoV-2 infection or tested positive for SARS-CoV-2 nucleic acid amplification were excluded from the study.
The researchers estimated 50% inhibitory serum dilutions (ID50s) in samples that were collected four weeks after administration of the BNT162b2 booster vaccine in a group of 30 healthcare workers and elderly participants. All eligible participants had a history of prior vaccination with two doses of BNT162b2 without incidence of intermittent SARS-CoV-2 infections.
In addition, we examined the activity of 17 different monoclonal antibodies licensed to treat SARS-CoV-2 infections by estimating their 50% inhibitory concentrations (IC50s).
Results of the study
Although the neutralizing activity against the Omicron SARS-CoV-2 sublineages was significantly lower than that of the B.1 sublineage, the variations between individual Omicron sublineages were less notable. The geometric mean ID50 values were 6,429, 1,725, 615, 1,052 and 1,203 against sublines B.1, BA.2, BA.4/5, BA.2.12.1 and BA.2.75, respectively. Compared to other Omicron sublines, serum anti-BA.2.75 activity was markedly lower compared to BA.2 and higher than BA.4/5.
Neutralization sensitivity of the BA.2.75 subline. (A) Fifty percent inhibitory dilutions (ID50s) against SARS-CoV-2 variants in samples collected four weeks after a BNT162b2 booster vaccination (n = 30) determined by a pseudovirus neutralization assay. Circles indicate mean ID50s from two experiments for each variant and individual participant. Bars and numbers indicate the ID50 geometric mean. Solid lines indicate 95% confidence intervals and the dashed line shows the lower limit of quantification. (B) Fifty percent inhibitory concentrations (IC50s) of monoclonal antibodies against SARS-CoV-2 variants determined by pseudovirus neutralization assay (mean IC50 of two experiments for each variant).
Most of the 17 monoclonal antibodies failed to effectively neutralize BA.2.12.1, BA.2, or BA.4/5.; however, most of these antibodies showed significant activity against BA.2.75. For example, antibodies such as regdanvimab and tixagevimab, which are licensed for the treatment and prevention of SARS-CoV-2 in South Korea, showed undetectable and poor activity, respectively, against Omicron sublines. However, these antibodies showed potent neutralization against BA.2.75.
Similarly, bebtelovimab also showed significantly potent neutralizing activity against BA.2.75. Overall, 30–35% of antibodies effectively neutralized BA.2.12.1, BA.2, or BA.4/5 sublineages, while 59% of antibodies neutralized BA.2.75.
Neutralizing activity of monoclonal antibodies. Fitted SARS-CoV-2 pseudovirus neutralization curves of monoclonal antibodies. Circles and bars represent mean values of two experiments (each performed with technical duplicates) and standard deviation. Dotted lines indicate 50% neutralization.
Conclusions
The results of the study indicate that the mutations detected in the spike protein of the SARS-CoV-2 Omicron BA.2.75 sublineage reduced the viral susceptibility to the neutralizing activity induced by the COVID-19 vaccines compared to BA. 2. In addition, BA.2.75 was more sensitive to SARS-CoV-2 neutralizing monoclonal antibodies, including those currently approved to treat COVID-19.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.