Vaccine-elicited immune pressure and SARS-CoV-2 mutational dynamics in breakthrough infections

Breakthrough infections post-vaccination raise concerns regarding vaccine efficacy and viral adaptability. This study examines the relationship between viral mutations, vaccine efficacy, and breakthrough infections in a cohort of 42 individuals positive for SARS-CoV-2 (Delta variant) from March to July 2022. The cohort included vaccinated (CovishieldTM n = 18, CovaxinTM n = 16) and unvaccinated individuals (n = 8). Sequencing and mutation analysis revealed higher mutation rates in vaccinated individuals. Immune escape mutations (T19R, L452R, T478K, D614G, P681R, and D950N) were prevalent among vaccinated individuals. The receptor binding domain (RBD) exhibited amino acid substitutions enhancing spike-ACE2 binding. Serum Spike-IgG was present in all patients, indicating acquired immunity. Consequently, enhanced immunological barriers in vaccinated individuals led to an elevated mutation rate as SARS-CoV-2 sought to evade immunity and augment spike protein-ACE2 receptor affinity. Identified mutations showed a negative correlation with kidney health, evidenced by higher serum creatinine levels (P = 0.0043). These findings underscore the potential implications for managing and responding to future outbreaks, highlighting the necessity for ongoing viral mutation surveillance and analysis.