The ongoing COVID-19 pandemic has made an unprecedented impact on global public health. A number of vaccines have been developed, of which two mRNA vaccines and adenovirus-vectored vaccine have been licensed or received emergency use authorization. While the rapid development of these first-generation vaccines provides hope, emergence of SARS-CoV-2 variants with enhanced transmission and/or disease severity has posed a constant challenge to the efficacy of the current vaccines. Our group has developed a dual mRNA spike and nucleocapsid vaccination approach that elicits broad protection against major SARS-CoV-2 variants of concerns. We will discuss protective efficacy of the mRNA vaccines against circulating and emerging SARS-CoV-2 variants well as the associated innate and adaptive immune mechanisms.