Immunological mechanisms of vaccine-induced protection against COVID-19 in humans

Abstract

Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. Several vaccines, including mRNA, adenoviral-vectored, protein subunit and whole-cell inactivated virus vaccines, have now reported efficacy in phase III trials and have received emergency approval in many countries. The two mRNA vaccines approved to date show efficacy even after only one dose, when non-NAbs and moderate T helper 1 cell responses are detectable, but almost no NAbs. After a single dose, the adenovirus vaccines elicit polyfunctional antibodies that are capable of mediating virus neutralization and of driving other antibody-dependent effector functions, as well as potent T cell responses. These data suggest that protection may require low levels of NAbs and might involve other immune effector mechanisms including non-NAbs, T cells and innate immune mechanisms. Identifying the mechanisms of protection as well as correlates of protection is crucially important to inform further vaccine development and guide the use of licensed COVID-19 vaccines worldwide.

Fig. 1. Comparison of antibody responses induced by different COVID-19 vaccines.

a | Vaccine immunogenicity based on antibody against the spike (S) protein of SARS-CoV-2 and/or against the receptor-binding domain (RBD) of the S protein relative to levels seen in convalescent serum. b | Vaccine immunogenicity based on neutralizing antibodies (NAbs) against SARS-CoV-2, again relative to levels seen in convalescent plasma. Relative antibody levels induced are indicated for seven COVID-19 vaccines where these data are available. To enable direct comparison, only vaccines tested in two-dose schedules are included. For antibody data, all comparisons are based on relative amount of antibody compared with human convalescent serum used in the same study (see data in Supplementary Table 1). Although the source of these samples differed between studies, these data enable reasonable direct comparisons between different vaccines, accounting for different assays used in different trials. In parts a,b, a ratio of one (black horizontal dashed line) indicates equivalence in amount of antibody between individuals who are vaccinated and average value for the relevant human convalescent serum — note logarithmic vertical axes. Where a range of data were reported for a specific parameter at a given time point (for example, between different age groups), the maximum reported value was used.