The COVID-19 pandemic is arguably the most important global threat to humankind that the world has seen in the 21st century. Since the initial outbreak of SARS-CoV-2 in 2019, the virus genome is continuously mutating that may affect virus characteristics such as infectivity, transmission, and pathogenicity. We recently found that two consecutive amino acid mutations R203K and G204R in the nucleocapsid (N) protein, are linked with higher viral load and severity in COVID-19 patients. Here, we performed comparative total proteomic analysis of HEK293T (stably expressing ACE2/TMPRSS2) cell lines infected with wildtype (WT) VLP, KR-mutant (KR) VLP with two mutations R203K/G204R in the nucleocapsid protein, and two additional controls D614G-KR (containing both R203K/G204R and spike D614G mutations) and D614G (only spike D614G mutation). Our data reveal enhanced expression of immune response proteins in KR VLP infected cells.