Neutralizing Antibodies against 10 SARS-CoV-2 Variants at Two Years Post-COVISHIELD Vaccination with Special Reference to Omicron Subvariants and Booster Administration.

To study the durability of neutralizing antibodies (NAbs) against ten SARS-CoV-2 variants among COVISHIELD vaccine recipients from Pune, India, 184 vaccinee samples with (pre-positives) or without (pre-negatives) prior antibody positivity were evaluated. To estimate NAb levels, a validated ten-plex MSD ACE2 neutralization assay was used. NAbs against Alpha, Beta, Delta, and Omicron/subvariants were assessed at 1 month (PD2-1) and 6 months (PD2-6) post-vaccination, post-booster dose, and 2 years (2Y) post-vaccination. In pre-negatives, the seropositivity declined from PD2-1 to PD2-6 for all variants (Omicron variants: 14-54% to 0%; non-Omicron variants: 66-100% to 8-44%). In pre-positives, the decline in seropositivity from PD2-1 to PD2-6 was seen only for Omicron variants (14-39%). At PD2-6, a significant reduction in NAb levels was observed in all vaccinees against all the variants. Irrespective of prior exposure, the diminished anti-variant antibody levels at PD2-6 increased significantly following the administration of the booster. In conclusion, the COVISHIELD vaccine booster dose did provide cross-neutralizing antibodies against broad-range SARS-CoV-2 variants with improved durability up to [16 (15-18)] months post-booster dose and two years post-vaccination.