Neutralizing possibilities of whole virion and mRNA vaccine triggered antibodies of Wuhan strain of SARS-CoV-2 with receptor binding domains of spike proteins of Delta and Omicron strains
Shilpa Barthwal , Bennet Angel , Annette Angel , Vinod Joshi , BM Shareef , Nuzhat M Peer , Poorna Khaneja , Ambreen S Khan , Bhawna Sharma , Neha Singh , Ramesh Joshi , Komal Tomar , Kiran Yadav , Satendra P Singh
Asian Pacific Journal of Tropical Medicine ›› 2023, Vol. 16 ›› Issue (2) : 92 -94.
Mutations in the receptor binding domain (RBD) of SARS-CoV-2 spike protein have given birth to the new variants of concern viz. Delta and Omicron strain. As we are using vaccines which are either mRNA of spike protein of Wuhan strain or its whole virion vaccine, these vaccines will trigger antibodies to be able to bind with the epitopes of spike protein of Wuhan strain. There appears a need to study whether vaccine generated circulating neutralizing antibodies in vaccinated people are able to neutralize the receptor binding domain of spike protein of currently circulating Delta and Omicron strains as well. We need to address this contention in two phases: first to undertake docking studies of vaccine generated antibodies with Wuhan, Delta and Omicron strains and second to conduct the wet lab studies and observe antigen-antibody bindings employing Immunofluorescence and Cryo-Electron Microscopic studies. The present paper reports results of docking studies using bioinformatic softwares to provide the baseline information for wet lab studies. The structures of two types of vaccine produced antibodies (Ab) were obtained from Research Collaboratory for Structural Bioinformatics Database Protein Data Bank (RCSB PDB). For whole virus inactivated vaccine (Vaccine 1), PDB ID 7WE9 and for mRNA vaccine (Vaccine 2), PDB ID 6XCA were used. Antibody of Vaccine 1 was in complex with spike protein of Omicron variant. The antibody structure was constructed using ABody Builder-ML tool. After downloading amino acid sequence of light chain and heavy chain in Fasta format and by using tool ABody Builder-ML, the antibody structure was built and further downloaded. The PDB Format of spike antigen of the 3 strains were also obtained viz. Wuhan strain (PDB ID 6VXX), Delta strain (PDBID 7W92) and Omicron strain (PDBID 7QO7). Docking was performed in Cluspro app in antibody mode in which antibody was used as receptor and antigen as ligand. After docking, the model structures were analyzed and the lowest energy score was selected. To analyze the antigen-antibody (Ag-Ab) interactions, Pymol software was used. In this, the Ag-Ab structure was drawn from the software and then values of site of binding of Ag-Ab were recorded and analyzed. The antibody generated for Vaccine 1 when docked with Wuhan strain PDB ID 6VXX showed the lowest energy score of -309.7 (Figure 1A). The same when done for Delta strain PDB ID 7W92 and Omicron strain PDB ID 7QO7 showed the lowest energy score of -317.3 (Figure 1B) and -956.4 respectively (Figure1C). In the Ag-Ab interaction studies, it was observed that Wuhan strain showed good binidng with vaccine generated antibodies; however, both Delta and Omicron strains did not show any binidng (Figure 1A-1C). The antibody generated by Vaccine 2 when docked with Wuhan strain PDB ID 6VXX showed the lowest energy score of -341.0 (Figure 1D). The same when done for Delta strain PDB ID 7W92 and Omicron strain PDB ID 7QO7 showed the lowest energy score of -374.2 (Figure 1E) and -375.0 respectively (Figure 1F). Vaccine generated antibodies also did not show binding with Delta and Omicron strains (Figure 1D-1F).
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