4.6 Article

SARS-CoV-2 vaccine breakthrough infections (VBI) by Omicron variant (B.1.1.529) and consequences in structural and functional impact

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CELLULAR SIGNALLING
卷 109, 期 -, 页码 -

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2023.110798

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SARS-CoV-2; Omicron (B; 1; 529); Delta breakthrough vaccine; Neutralizing antibody

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This study examined the effectiveness of existing vaccines against hospitalization and infection caused by the Omicron variant of COVID-19, specifically for individuals who received two doses of Moderna or Pfizer vaccines and one dose of Johnson & Johnson vaccine or who were vaccinated more than five months ago. The presence of 36 variants in Omicron's spike protein, which is targeted by all three vaccines, has reduced the efficacy of antibodies in neutralizing the virus. Genetic sequencing of the SARS-CoV-2 viral sequence identified clinically significant variants, including E484K, that may pose a risk of infection despite successful immunization.
This study investigated the efficacy of existing vaccines against hospitalization and infection due to the Omicron variant of COVID-19, particularly for those who received two doses of Moderna or Pfizer vaccines and one dose of Johnson & Johnson vaccine or who were vaccinated more than five months before. A total of 36 variants in Omicron's spike protein, targeted by all three vaccinations, have made antibodies less effective at neutralizing the virus. The genotyping of the SARS-CoV-2 viral sequence revealed clinically significant variants such as E484K in three genetic mutations (T95I, D614G, and del142-144). A woman showed two of these mutations, indicating a potential risk of infection after successful immunization, as recently reported by Hacisuleyman (2021). We examine the effects of mutations on domains (NID, RBM, and SD2) found at the interfaces of the spike domains Omicron B.1.1529, Delta/B.1.1529, Alpha/B.1.1.7, VUM B.1.526, B.1.575.2, and B.1.1214 (formerly VOI Iota). We tested the affinity of Omicron for ACE2 and found that the wild-and mutant-spike proteins were using atomistic molecular dynamics simulations. According to the binding free energies calculated during mutagenesis, the ACE2 bound Omicron spikes more strongly than the wild strain SARS-CoV-2. T95I, D614G, and E484K are three substitutions that significantly contribute to RBD, corresponding to ACE2 binding energies and a doubling of the electrostatic potential of Omicron spike proteins. The Omicron appears to bind to ACE2 with greater af-finity, increasing its infectivity and transmissibility. The spike virus was designed to strengthen antibody immune evasion through binding while boosting receptor binding by enhancing IgG and IgM antibodies that stimulate human & beta;-cell, as opposed to the wild strain, which has more vital stimulation of both antibodies.

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