Variations in cross-neutralizing reactivity is dependent on mutations on immunogenic epitopes in the spike protein of SARS-CoV-2 variants.

Purpose

The COVID-19 pandemic has witnessed the rapid evolution of the SARS-CoV-2 virus, resulting in the emergence of multiple variants with mutations in critical regions of the spike protein, notably in the receptor binding domain. These mutations can lead to immune evasion and breakthrough (BT) infections, even in the vaccinated individuals. While previous studies have documented various mutations, there is a limited understanding of these mutations in different epitopes and their influence on the vaccine elicited immune response.

Methods

Neutralizing antibodies were detected using Plaque reduction neutralization test and peptide enzyme linked immunosorbent assay was standardized to identify possible epitopes contributing to immune escape. We used GraphPad Prism 9.5.0 (525) for analysis. Results were significant at p < 0.05.

Results

In this study, we observed that individuals with hybrid immunity, defined as immunity derived from both the natural infection and vaccination, exhibit significantly higher levels of neutralizing antibodies than individuals who had been solely vaccinated with COVISHIELD. Consequently, we highlight the substantial differences in the reactivity of neutralizing antibodies against the Wuhan, Delta, and Omicron variants. Our findings indicate that individuals who have recovered from COVID-19 and/or who experienced BT infections, showed stronger reactivity toward the conserved peptides than individuals vaccinated with no prior exposure.

Conclusions

COVISHIELD induced antibodies effectively neutralized original Wuhan strain but showed reduced neutralization against Delta and Omicron due to mutations in specific epitopes within their spike proteins. Mutations in variant specific epitopes can lead to evasion of the virus, emphasizing the importance of targeting linear region epitopes as critical binding sites.