The COVID-19 Vaccine Landscape.

The history of vaccine development spans centuries. At first, whole pathogens were used as vaccine agents, either inactivated or attenuated, to reduce virulence in humans. Safety and tolerability were increased by including only specific proteins as antigens and using cell culture methods, while novel vaccine strategies, like nucleic acid- or vector-based vaccines, hold high promise for the future. Vaccines have generally not been employed as the primary tools in outbreak response, but this might change since advances in medical technology in the last decades have made the concept of developing vaccines against novel pathogens a realistic strategy. Wandering the uncharted territory of a novel pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we can learn from other human Betacoronaviridae that emerged in the last decades, SARS-CoV-1 and MERS-CoV. We can identify the most likely target structures of immunity, establish animal models that emulate human disease and immunity as closely as possible, and learn about complex mechanisms of immune interaction such as cross-reactivity or antibody-dependent enhancement (ADE). However, significant knowledge gaps remain. What are the correlates of protection? How do we best induce immunity in vulnerable populations like the elderly? Will the immunity induced by vaccination (or by natural infection) wane over time? To date, at least 149 vaccine candidates against SARS-CoV-2 are under development. At the time of writing, at least 17 candidates have already progressed past preclinical studies (in vitro models and in vivo animal experiments) into clinical development. This chapter will provide an overview of this rapidly developing field.