Evidence for antibody as a protective correlate for COVID-19 vaccines

ABSTRACT

Though eleven novel COVID-19 vaccines have demonstrated efficacy, additional affordable, scalable, and deliverable vaccines are needed to meet unprecedented global demand. With placebo-controlled efficacy trials becoming infeasible due to the roll out of licensed vaccines, a correlate of protection is urgently needed to provide a path for regulatory approval of novel vaccines. To assess whether antibody titers may reasonably predict efficacy, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy ({rho}= 0.79) and binding antibody titer and efficacy ({rho} = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. This correlation is strengthened by substituting post-hoc analyses for efficacy against the ancestral strain (D614G), where available. Together with an accumulating body of evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.