Erosion of SARS-CoV-2 Vaccine Epitopes in Goa, India (2020–2025): A Five-Wave Analysis of T Cell and Antibody Target Mutations

Version 1.1 (June 2026): Corrections to figure placement and table formatting. All scientific findings, data, and conclusions are unchanged from v1.0. This is the first systematic analysis of SARS-CoV-2 vaccine epitope erosion across five pandemic waves in Goa, India, using 1,232 validated human T cell epitopes from the Immune Epitope Database (IEDB) and 495 good-quality Nextclade-analysed genome sequences (GISAID EpiCoV; EPI_SET_260610gh). T cell epitopes cover 1,273 of 1,274 spike amino acid positions (99.9%). Epitope disruption increased 9.9-fold from Wave 1 ancestral/Alpha sequences (mean 3.8 disrupted positions) through Delta (mean 8.0) to Omicron (mean 29.4) and XBB-era sequences (mean 37.6). The Delta-to-Omicron transition was the single largest immunological inflection point, representing a 3.7-fold jump in disrupted positions. Antibody epitope class disruption was near-universal for Class 2 RBD epitopes (96.6%), the furin cleavage site (99.2%), and the NTD supersite (74.5%). HR1 and CH/CD S2 subunit domains showed the lowest disruption across all variant groups, identifying them as priority targets for next-generation pan-variant vaccine design. This paper constitutes Paper 3 of a comparative genomic surveillance series for the West Coast and Western Ghats corridor of India. Paper 1: https://doi.org/10.5281/zenodo.20632518. Paper 2: https://doi.org/10.5281/zenodo.20647945. We gratefully acknowledge all data contributors, i.e., the Authors and their Originating laboratories responsible for obtaining the specimens, and their Submitting laboratories for generating the genetic sequence and metadata and sharing via the GISAID Initiative, on which this research is based. The GISAID Supplemental Table listing all originating and submitting laboratory data contributors is deposited with Paper 1 of this series (https://doi.org/10.5281/zenodo.20632518). GISAID citations: Elbe and Buckland-Merrett (2017) doi:10.1002/gch2.1018; Shu and McCauley (2017) doi:10.2807/1560-7917.ES.2017.22.13.30494; Khare et al. (2021) doi:10.46234/ccdcw2021.255