BackgroundDespite having an effective COVID-19 vaccine, the COVID-19 pandemic is far from over and the delta variant continues to cause havoc across several continents. The present study was conducted to analyze and describe the occurrence of COVID-19 cases among completely vaccinated individuals. MethodsIn an educational institute in Western Maharashtra, we analyzed a cluster of RTPCR positive COVID-19 cases among fully vaccinated students which occurred in 12 days. The cases were linked to a series of curricular and co-curricular events in the institute. A detailed epidemiological investigation and genome sequencing of cases were conducted. IgG antibodies against S1 protein of novel SARS-CoV-2 were estimated for cases and age, sex, and vaccination status matched controls. ResultsAll 37 identified cases were mild COVID. 188 high risk (HR) contacts of the cases were identified. The overall secondary attack was 9.5%. Out of 31 cases and 50 controls, 09 (29%) cases and 08 (16%) controls were found to have IgG antibodies against S1 protein of novel SARS-CoV-2 titer of more than 60 U/ml. Whole-genome sequencing of 15 samples of the cluster showed the presence of the Delta variant of SARS-CoV-2. No correlation was observed between Ct value and IgG S1 antibody titers. ConclusionThe study provides significant evidence that only vaccination alone does not completely protect against SARS-CoV-2 B.1.617.2 (Delta) variant infection. An all-encompassing multicomponent strategy involving implementation of NPIs, robust contact tracing, early identification and isolation of cases, and high vaccination coverage is the way forward for the prevention of COVID-19.