SARS-CoV-2, the virus that causes COVID-19, represents the third coronavirus to emerge as a global health threat in the past two decades, along with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). With the expanding number of coronaviruses being discovered in reservoirs, emergence of novel coronaviruses into humans is imminent. Thus, coronaviruses that are closely related to MERS-CoV are still a pandemic threat. To that end, we are exploring the antigenic landscape of vaccine-induced immunity to MERS-CoV spike by defining mechanisms of action and protective capacity of B-cell and antibody responses that target non-classical areas of the spike protein. The goal is to understand which areas of the MERS-CoV spike protein are most optimal for eliciting robust, broad, and long-lasting immune responses. This research will lead to next-generation MERS-CoV vaccine designs that can be deployed shall a MERS-like outbreak occur.