The immunology of SARS-CoV-2 infections and vaccines

Abstract

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.

Keywords: COVID-19; Systems vaccinology; Vaccines.

Fig. 1

COVID-19 vaccine candidates in clinical evaluation to date. Numbers represent the number of vaccine candidates of that platform technology currently in clinical testing.

Fig. 2

Current vaccine platforms of COVID-19 vaccine candidates.

Fig. 3

Human challenge study of coronavirus 229E (Callow, 1990 [22]). 15 volunteers were inoculated with 229E, 10 of whom became infected. Chart shows average antibody titers in the infected and infected groups. All subjects were rechallenged, and all originally uninfected patients got infected upon secondary exposure, compared to 6 out of the 9 patients who were originally infected.

Fig. 4

The innate immune response in mild and severe COVID-19 patients. Severe COVID-19 cases appear to have refractory innate immune responses in blood, suggesting a spatial dichotomy in the innate immune response, whereby peripheral innate cells can be inhibited in the face of inflammatory responses reported in the lungs.

Fig. 5

The durability of antibody responses over time in 4 different infection/vaccination scenarios.

Fig. 6

Systems vaccinology approaches for accelerating the vaccine-testing pipeline.