From mutation to escape, is the Omicron BA.1 vaccine still useful?

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It has been more than two years since the outbreak of the COVID-19 epidemic, and human production and life have been severely affected. The successive emergence of Omicron variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 poses a serious challenge to the preventive effect of vaccination and the treatment of antibody drugs. With the accelerated global spread of the Omicron variant subtype, WHO is considering recommending a new vaccine with an improved version of Omicron as a booster.

However, recently, researchers from Peking University Biomedical Sciences found that the new subtypes of Omicron mutant strains BA.2.12.1, BA.4, and BA.5 showed strong immune evasion ability, and were resistant to Omicron BA. .1 Significant neutralization escape occurred in plasma after recovery from infected persons.

In fact, at present, the main Omicron mutants all have high transmission ability. In order to study the relationship between their transmission ability and the conformation of spike protein and receptor binding ability, the research team analyzed the Omicron mutant BA. .2, BA.3, BA.2.12.1, BA.2.13 and BA.4, BA.5 spike protein trimers of the cryo-EM structure, and the mutant spike protein or receptor binding domain ( RBD) affinity to hACE2.

The results showed that the affinity of BA.2.12.1, BA.2.13 and BA.4, BA.5 for hACE2 was comparable to that of BA.2. The F486V mutation carried by BA.4 and BA.5 may lead to a decrease in the affinity of hACE2, but L452R and 493Q Back mutations reduced this effect.

In addition, the study determined the escape mutation spectrum, epitope distribution and neutralization effect of 1640 viral receptor-binding domain RBD-directed antibodies, and then found that the original strain of COVID-19 as well as the BA of Omicron The .1 strain produced cross-immunized neutralizing antibodies largely escaped by BA.2, BA.4, and BA.5, and produced weaker immune responses to variants that predate Omicron.

It is worth mentioning that for those who have been infected with the original COVID-19 strain or the Alpha variant early and received three doses of the mRNA vaccine, when re-infected with the Omikron strain, the ability to target Omikron is weakened. The immune response of the strain. For those who have not been infected with COVID-19 before, but have received three doses of the mRNA vaccine, infection with the Omicron strain will have an immune-enhancing effect.

At present, Pfizer/BioNTech and Moderna are developing a new version of the booster vaccine against the Omicron variant. However, based on the poor immunogenicity of the early variant of Omicron, it is unknown whether the booster vaccine has advantages.