We have experienced an enormous cohesive effort of the scientific community to understand how the immune system reacts to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how to elicit protective immunity via vaccination. This effort resulted in the development of vaccines in record time with high levels of safety, efficacy, and real-life effectiveness. However, the rapid diffusion of viral variants that escape protective antibodies prompted new studies to understand SARS-CoV-2 vulnerabilities and strategies to guide follow-up actions to increase, and maintain, the protection offered by vaccines. In this review, we report the main findings on human immunity to SARS-CoV-2 after natural infection and vaccination; we dissect the immunogenicity and efficacy of the different vaccination strategies that resulted in products widely used in the population; and we describe the impact of viral variants on vaccine-elicited immunity, summarizing the main discoveries and challenges to stay ahead of SARS-CoV-2 evolution. SIGNIFICANCE STATEMENT: This study reviewed findings on human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyzed the immunogenicity and efficacy of the various vaccines currently used in large vaccination campaigns or candidates in advanced clinical development, and discussed the challenging task to ensure high protective efficacy against the rapidly evolving SARS-CoV-2 virus. This manuscript was completed prior to the emergence of the Omicron variant and to global vaccine boosting efforts.
Copyright © 2022 The Author(s).