Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates. Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated. Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil. Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.