SARS-CoV-2 omicron variant may evade host immune responses

A recent study conducted at the Medical University of Innsbruck, Austria, has demonstrated that the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a higher ability to evade antibody-mediated neutralization than other variants of concern (VOCs), including alpha, beta, and delta variants.

Study: SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals. Image Credit: FOTOGRIN/ShutterstockStudy: SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals. Image Credit: FOTOGRIN/Shutterstock

The study is currently available on the medRxiv* preprint server, whilst the article undergoes peer review

Background

With the progression of the coronavirus disease 2019 (COVID-19) pandemic, several potentially severe variants of SARS-CoV-2 have emerged. Some of these variants have acquired escape mutations in the spike protein that are associated with improved viral fitness in terms of increased infectivity, transmissibility, pathogenicity, and immune evasion. These variants were designated as VOCs by the World Health Organization (WHO).
 

The most recently emerged VOC is the B.1.1.529 (omicron) variant of SARS-CoV-2. The omicron variant, which was first identified in South Africa in November 2021, has already been identified in 63 countries across the globe, including the US and UK. Preliminary evidence suggests that the omicron variant might be more infectious than the previously dominant delta variant. However, not enough information is so far available to determine whether the variant can escape neutralization by infection- or vaccination-induced antibodies. The whole-genome sequencing studies have shown that the omicron variant is heavily mutated, with 26 – 32 mutations in the spike protein.

In the current study, scientists have investigated the ability of anti-SARS-CoV-2 antibodies in neutralizing the omicron variant. They have also compared the immune escape ability of the omicron variant with other VOCs, including the alpha, beta, and delta variants.

Study design

For virus neutralization assay, the scientists collected serum samples from individuals infected with the alpha, beta, and delta variants of SARS-CoV-2. For vaccination-induced antibodies, they collected serum samples from individuals fully immunized with the mRNA-based (Moderna and Pfizer/BioNTech) or adenoviral vector-based (Oxford/AstraZeneca) COVID-19 vaccines. To test the immune responses of heterologous prime-boost immunization, they collected samples from individuals who had received AstraZeneca prime/Pfizer boost vaccination.

The scientists conducted focus forming assay with replication-competent SARS-CoV-2 viruses to determine neutralizing antibody titers against alpha, beta, delta, and omicron variants.

In a separate set of experiments, they analyzed the neutralization potency of super immune sera against the delta and omicron variants. The super immune sera were collected from individuals who were previously infected and subsequently vaccinated, or those who were previously vaccinated and subsequently infected (vaccine breakthrough cases).

Important observations

The Moderna and AstraZeneca vaccines showed significantly lower neutralizing ability against the omicron variant compared to that against other tested variants. However, the Pfizer vaccine and heterologous AstraZeneca/Pfizer vaccines showed comparatively higher neutralization against the omicron variant compared to other tested vaccination regimens.

In contrast, antibodies induced by natural SARS-CoV-2 infection largely failed to neutralize the omicron variant. However, the antibodies showed potent neutralizing ability against the alpha, beta, and delta variants.

Importantly, super immune antibodies showed considerable neutralizing efficacy against the omicron variant. However, the efficacy was comparatively higher against the delta variant.

Study significance

The study findings indicate that the omicron variant of SARS-CoV-2 can significantly escape host immune responses induced by natural infection or vaccination. Compared to homologous immunization with an adenoviral vector-based vaccine, heterologous prime/boost immunization with adenoviral vaccine and mRNA vaccine exhibits higher efficacy in neutralizing the omicron variant.

As observed in the study, individuals who had both infection and vaccination are potentially protected against the omicron variant. As mentioned by the scientists, it is important to develop variant-specific vaccines to provide the highest protection against newly emerging SARS-CoV-2 variants.

*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.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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