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Published on: May 2, 2011
EFFECT OF RBD MUTATIONS IN SPIKE GLYCOPROTEIN OF SARS-COV-2 ON NEUTRALIZING IGG AFFINITY
T Hayashi1, N Yaegashi2, I Konishi3
11National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 2START, Japan Science and Technology Agency (JST), Tokyo, Japan.
Abstract:
Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subvariants (B.1.1.7, B.1.351, and B.1.1.248) and omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants. We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F, N501Y or the mutants of RBD of omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants on neutralizing antibodies in serum derived from individuals including children (aged 5-11 years) inoculated with mRNA based COVID-19 vaccine (BNT162b2: Pfizer/BioNTech) or COVID-19-positive patients or children (aged 5-11 years) after vaccination with BNT162b2. Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients. The significantly low antibody titer of children against Omicron type SARS-CoV-2 BQ.1.1 subvariant and XBB.1.16 subvariant in Japan. Infection with SARS-CoV-2 subspecies that causes serious symptoms in humans may spread globally. In particular, since the antibody titer against the omicron type is low in children (aged 5-11 years) who have been vaccinated with conventional vaccines, therefore it is important for children to receive vaccines specific for the omicron type.
Insights
Mutant SARS-CoV-2 strains like Y453F and N501Y show partial immune escape. Children vaccinated with mRNA vaccines have low antibody titers against Omicron variants, highlighting the need for updated vaccines.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Certain SARS-CoV-2 receptor binding domain (RBD) mutants, such as Y453F (linked to mink transmission) and N501Y (found in major variants and Omicron subvariants), are significant for viral spread.
- Understanding the characteristics of these RBD mutants and their impact on neutralizing antibodies is crucial for public health strategies.
Purpose of the Study:
- To investigate the structural characteristics of SARS-CoV-2 RBD mutants Y453F and N501Y.
- To evaluate the effect of Y453F, N501Y, and Omicron (BQ.1.1, XBB.1.16) RBD mutants on neutralizing antibodies in vaccinated individuals and COVID-19 patients, with a focus on children aged 5-11 years.
Main Methods:
- Three-dimensional structural analysis of RBD mutants Y453F and N501Y.
- Assessment of neutralizing antibody activity in serum samples from vaccinated individuals (BNT162b2) and COVID-19 patients against various SARS-CoV-2 RBD mutants.
Main Results:
- SARS-CoV-2 strains with Y453F or N501Y RBD mutations demonstrated partial immune evasion against monoclonal and polyclonal neutralizing antibodies from COVID-19 patients.
- Significantly lower antibody titers were observed in children (aged 5-11 years) vaccinated with conventional mRNA vaccines against the Omicron BQ.1.1 and XBB.1.16 subvariants.
Conclusions:
- The Y453F and N501Y RBD mutations contribute to SARS-CoV-2 immune escape.
- Current mRNA vaccines may offer limited protection against Omicron subvariants in children, emphasizing the urgent need for Omicron-specific vaccines for this age group to enhance protection against severe disease.
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