Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination

Abstract

Background Several SARS-CoV-2 lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as Variants of Concern (VOCs) or Variants of Interest (VOIs). Here, we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant) which were first detected in India and the Philippines, respectively. Methods The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1 and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from COVID-19 patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum IgG binding to wild type and mutant RBDs were determined using an enzyme immunoassay. Results The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4-5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4-7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.671.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. Conclusion P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with one variant do not confer cross protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and “non-variant” strains.

Application of omics technology to combat the COVID‐19 pandemic

“… 48 , 49 P.3 variant (B.1.1.28.3), which carried N501Y and E484K on the RBD of S protein, is another sub‐lineage prevalent in Philippines. 50 , 51 …”

Extracellular pH, osmolarity, temperature and humidity could discourage SARS-CoV-2 cell docking and propagation via intercellular signaling pathways

“…Due to the high rate of mutations and emerging new variants, vaccines may need to be adapted to ensure protection. Some data raise concerns on the level of protection provided by COVID-19 vaccines against some variants Krishnan & Krishnan, 2021;Chen et al, 2021;Baj et al, 2021). Amino acid substitutions in the spike protein (S-protein) are an important virus strategy to evade the host immune response.…”

In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn

“…Recombinant Gn (residues 21-452) of the SFTSV membrane glycoprotein polyprotein from the reference sequence severe fever with thrombocytopenia syndrome virus (GenBank accession no. AZZ69059.1) was expressed and purified in insect cells as we described previously with modifications [29]. Briefly, Gn gene sequences were baculoviruscodon-optimized and cloned into pFast dual baculovirus expression vector.…”

“…ELISA-based binding competition assay was used to confirm the binding of peptide HKU-P1 to the SFTSV Gn protein. The SFTSV Gn protein was expressed (Figure 2B) and purified using baculovirus expression system, and the protein was coated onto ELISA immune plate [29]. We first tested whether biotin-HKU-P1 could bind to the SFTSV Gn protein.…”