Monoclonal antibody activity against SARS-CoV-2 Omicron variant

Scientists from Germany have recently pointed out that the third booster dose of mRNA-based coronavirus disease 2019 (COVID-19) vaccine is highly effective in neutralizing the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study is currently available on the medRxiv* preprint server.

Study: mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Image Credit: Viacheslav Lopatin/Shutterstock

Background

The omicron variant of SARS-CoV-2 was first detected in South Africa in November 2021. Soon after its emergence, the variant has spread rapidly in many countries across the globe, indicating its increased transmissibility. Given its predominance, the World Health Organization has designated the omicron variant as a variant of concern (VOC).

Compared to other VOCs (alpha, beta, gamma, and delta variants), the omicron variant is heavily mutated, with around 35 mutations in the spike protein and 15 mutations specifically in the spike receptor-binding domain (RBD). Some of these mutations are present in the key epitopes of neutralizing antibodies, indicating the possibility of immune escape.

Most currently approved COVID-19 vaccines contain the original Wuhan strain spike protein of SARS-CoV-2 as a vaccine antigen. Thus, there is a possibility that these vaccines may have reduced efficacy in neutralizing mutated variants of SARS-CoV-2, including the omicron variant.

In the current study, the scientists have explored the efficacy of infection- or vaccination-induced antibodies in neutralizing the omicron variant.

Study design

The scientists collected serum samples from 30 individuals who had received two doses of the Pfizer mRNA vaccine one month before. The samples were used to neutralize the omicron variant using a pseudovirus neutralization assay. The neutralizing efficacy of a third booster dose of the same vaccine was also determined in the study.

In addition, the scientists collected serum samples from 30 COVID-19 recovered individuals 1.5 months and 12 months after disease diagnosis. The samples were used to determine the efficacy of infection-induced antibodies in neutralizing the omicron variant. To explore the impact of a combination of infection and vaccination, they collected a separate set of samples from these individuals one month after receiving the first dose of the Pfizer vaccine.

Impact of vaccination against omicron variant

The analysis of vaccinated serum samples revealed that antibodies induced by mRNA-based COVID-19 vaccines have the highest neutralizing efficacy against wild-type SARS-CoV-2 (Wuhan strain), followed by the alpha, delta, and beta variants. In contrast, only 27% of samples showed neutralizing antibodies against the omicron variant. However, the antibody titers against the omicron variant were significantly lower than those against other tested variants.

Regarding the durability of vaccine immunity, a 4-fold reduction in neutralizing titers against wild-type virus was observed five months after two-dose vaccination. However, the titers increased significantly one month after the third booster dose. Importantly, the booster dose in all 30 vaccine recipients caused a 100-fold induction in neutralizing titers against the omicron variant.

Impact of infection against omicron variant

A significantly high neutralizing titer against wild-type virus was observed at the early phase of recovery (1.5 after infection). However, the titers decreased significantly after 12 months. After one month of first-dose vaccination, all COVID-19 recovered individuals showed a sharp increase in neutralizing titer against wild-type virus.

Almost all convalescent samples showed weak neutralizing efficacy at both early and late time points regarding the omicron variant. Importantly, a single dose of mRNA vaccine caused a robust increase in neutralizing titer against the omicron variant in all convalescent individuals.  

Impact of monoclonal antibodies against omicron variant

The omicron neutralizing efficacy of nine monoclonal antibodies was tested in the study. Some of these antibodies are approved for clinical use, including bamlanivimab, etesevimab, casirivimab, imdevimab, and sotrovimab.

All tested antibodies showed neutralizing titers against wild-type virus and alpha variant. However, only 7 and 5 out of 9 antibodies showed neutralizing efficacy against the delta and beta variants, respectively.

Seven out of 9 antibodies failed to induce neutralizing antibodies regarding the omicron variant.

Study significance

The study findings reveal that the two-dose immunization with mRNA-based COVID-19 vaccines is insufficient to prevent the omicron variant of SARS-CoV-2. Similarly, antibodies developed in response to natural SARS-CoV-2 infection largely fail to neutralize the variant.

Importantly, the study highlights that a third booster dose of mRNA vaccine is highly efficient in neutralizing the omicron variant. Similarly, a single-dose vaccination in COVID-19 recovered individuals is sufficient to prevent omicron infection.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.