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COVID-19 (Coronavirus disease 2019 or severe acute respiratory syndrome coronavirus 2) is a transmissible illness affected by a virus of the Coronaviridae family. Omicron is one of the COVID-19 variants of SARS-CoV-2 that firstly informed from Botswana B.1.1.529 was the original subvariant of omicron and then numerous sub-variants of Omicron have appeared comprising: BA.1, BA.2, BA.3, BA.4, and BA.5, BQ.1 and BQ.1.1, XBB.1, and XBB 1.5. The aim of this in silico research is to investigate the effect of monovalent (monovalent) vaccines on the XBB.1.5 variant. In this in silico study the sequence of spike protein obtained from NCBI and then the mutations of XBB 1.5 were add to obtained sequence. Since most of the currently used vaccines belong to the RBD region, in this study the RBD mutations were analyzed. All B cell and T cell epitopes of original strain (Wuhan) recorded and the epitopes that changed via mutation (XBB 1.5) were removed. The original virus has 10 B-cell epitopes in the RBD region. 5 of these epitopes were not mutated (unchanged. Besides the B cells epitopes, 45 alleles of T cell epitopes were also unchanged. The result of this study informed that the monovalent vaccine can produce humoral and especially cellular immunity and the vaccines help protect against severe illness, hospitalization, and death. The mutations will certainly reduce the effectiveness of monovalent vaccine, so the use of bivalent vaccines is recommended. Some countries do not have bivalent vaccines; these countries can still use monovalent vaccines.

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