SARS-CoV-2, the virus that causes COVID-19, emerged in late 2019, and was declared a global pandemic on March 11th 2020. With over 50 million cases and 1.2 million deaths around the world, to date, this pandemic represents the gravest global health crisis of our times. Thus, the race to develop a COVID-19 vaccine is an urgent global imperative. At the time of writing, there are over 165 vaccine candidates being developed, with 33 in various stages of clinical testing. In this review, we discuss emerging insights about the human immune response to SARS-CoV-2, and their implications for vaccine design. We then review emerging knowledge of the immunogenicity of the numerous vaccine candidates that are currently being tested in the clinic and discuss the range of immune defense mechanisms that can be harnessed to develop novel vaccines that confer durable protection against SARS-CoV-2. Finally, we conclude with a discussion of the potential role of a systems vaccinology approach in accelerating the clinical testing of vaccines, to meet the urgent needs posed by the pandemic.