Principles Learned from the International Race to Develop a Safe and Effective COVID-19 Vaccine

Abstract

Vaccines against COVID-19 have the potential to protect people before they are exposed to the infective form of the virus. However, because of the involvement of pathogenic immune processes in many severe presentations of COVID-19, eliciting an immune response with a vaccine must strike a delicate balance to achieve viral clearance without also inducing immune-mediated harm. This Outlook synthesizes current laboratory findings to define which parts of the immune system help with recovery from and protection against the virus and which can lead to adverse outcomes. To inform our understanding, we analyze research about the immune mechanisms implicated in SARS-CoV, from the 2003 outbreak, and SARS-CoV-2, the virus causing COVID-19. The impact of how innate immunity, humoral immunity, and cell-mediated immunity play a role in a harmful versus helpful response is discussed, establishing principles to guide the development and evaluation of a safe but effective COVID-19 vaccine. The principles derived include (i) targeting the appropriate specificity and effector function of the humoral response, (ii) eliciting a T cell response, especially a cytotoxic T cell response, to achieve safe, yet effective, immune protection from COVID-19, and (iii) monitoring for the possibility of acute lung injury during SARS-CoV-2 infection post-vaccination in preclinical and clinical studies. These principles can not only guide efforts toward a safe and effective COVID-19 vaccine, but also the development of effective vaccines for viral pandemics to come.

Figure 1

Immune response to SARS-CoV-2 infection. Activation of inflammatory macrophages and subsequent production of proinflammatory cytokines is associated with adverse outcomes, including lung injury, during SARS-CoV-2 infection. Antibodies from humoral immunity can link adaptive immunity and innate immunity through Fc receptor interactions, leading to inflammatory activation of macrophages. Humoral immunity can also help promote viral clearance when targeted to appropriate parts of the virus. T cells have been shown to play an important role in viral clearance and recovery. CD8+ cytotoxic T cells, in particular, have been associated with favorable outcomes. Helper T cells can be of the Th1 subtype, which promote T cell activity, or the Th2 subtype, which link cell-mediated and humoral immunity by promoting B cell activity.