The vaccines on the market are based on the spike protein of the original SARS-CoV-2 strain, which was discovered in Wuhan, China, in 2019. Antibodies against the spike proteins, as well as T cell responses, are elicited by these vaccines, which protect against serious infection.

The SARS-CoV-2 virus has evolved due to mutations in the viral genome since the start of the COVID-19 outbreak. In comparison to the original strain, the newly emerging SARS-CoV-2 strains are more communicable and aggressive. Furthermore, some of the mutations are immune to the immunological responses elicited by COVID-19 vaccines and wild infections.

Extensive genomic surveillance has revealed the appearance of thousands of individual COVID-19 virus genome mutations in a lot of different places. Certain SARS-CoV-2 types, including Alpha, Beta, Gamma, and Delta, include mutations in the spike protein’s Receptor Binding Motif (RBM). According to the SARS-CoV-2 infection mechanism, the spike protein interacts with the host cell’s ACE2, resulting in membrane fusion and infection.

Earlier studies have found that mutations in the spike region increase the rate of transmission by increasing the virus’ affinity for ACE2 or allowing immune escape. These variants have been labeled as “variants of concern” (VOC). The Delta variant of SARS-CoV-2 is currently the most widely circulating strain.

Another new VOC, Omicron (B.1.1.529), has recently been identified from South Africa. Because of its high transmission rate, this variation has sparked more alarm among scientists. According to recent South African studies based on the Omicron type, this variant can infect a population in which 60-80 percent of people have had a previous COVID-19 infection or immunization.

Although these studies showed that Omicron can cause breakthrough infections, they did not show that the infection can progress to a more serious stage.

In comparison to other VOCs, scientists discovered that Omicron had a large number of mutations in the spike protein. It contains thirty amino acid changes, six residue deletions, and three residue insertions. The mutations are mostly concentrated in the RBM area. This could explain why Omicron has such a high affinity for ACE2, reducing the neutralizing activity of RBM-binding antibodies whose primary goal is to prevent ACE2 interaction.

Furthermore, mutations have also been discovered in the spike protein’s Receptor Binding Domain (RBD) and N-Terminal Domain. Many changes in the spike area are thought to be responsible for the increased affinity for ACE2 and antibody evasion.

In general, scientists are doubtful that the Omicron strain may infect people who have been vaccinated. However, a new study published on the medRxiv* preprint server used an Omicron isolate collected from patients in the United Kingdom to undertake neutralization testing.

Sera samples from healthy vaccinated individuals who received two doses of the Oxford-AstraZeneca (AZD1222) vaccine or the Pfizer-BioNTech (BNT162b2) vaccine were used to perform neutralizing assays in this investigation. Four weeks after the second dose of vaccine, which was given 8-11 weeks following the first, samples were taken.

This study cohort comprised twenty-two participants who received the AZD1222 vaccine and twenty-one participants who received the BNT162b2 vaccine.

Scientists compared neutralization titers against Omicron with neutralization titers against Victoria (SARS-CoV-2/human/AUS/VIC01/2020), an early Wuhan-related isolate, and the Beta, and Delta variants.

In this investigation, all but one participant’s neutralizing titers in sera samples from people who received the homologous AZD1222 vaccine fell below the detectable threshold.

Furthermore, in the case of the Omicron type, the median neutralizing titers of sera samples from patients who received homologous BNT162b2 decreased dramatically. Against the Victoria strain, however, the neutralizing titer remained high.

The authors are testing the efficiency of the COVID-19 booster approach against the Omicron variant in a current trial. This would aid in determining the efficacy of the booster vaccination strategy in terms of severity of illness and virus transmission for the newly developed variant of concern. According to the authors, immunological escape could lead to Omicron displacing the Delta strain and becoming the dominant strain globally. To protect people from infection in this scenario, a new vaccination tailored particularly for the Omicron strain must be developed.

Scientists are considering switching from monovalent vaccine design to multivalent vaccine formulations, which are currently used for influenza, due to the ineffectiveness of immunizations against the Omicron strain. At this time, timely vaccination of the unvaccinated group remains the top goal for reducing transmission and infection severity.

*Preliminary scientific papers published on medRxiv are not peer-reviewed and should not be regarded as conclusive, should not be used to guide clinical practice or health-related behavior, and should not be recognized as established information.

*Source: 10.1101/2021.12.10.21267534v1

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