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

Abstract

A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably predict efficacy and serve as the basis of a CoP, 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 (ρ = 0.79) and binding antibody titer and efficacy (ρ = 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. Together with 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.

A correlate of protection for SARS-CoV-2 vaccines is urgently needed

“…Notably, correlates may differ depending on the endpoint used, such as protection from infection, from disease, from severe disease or from mortality. Two studies, by Khoury et al 3 (published in this issue of Nature Medicine) and Earle et al 4 , now connect neutralizing antibody responses to SARS-CoV-2 with vaccine efficacy and bring researchers and clinicians closer to having a correlate of protection for vaccines against COVID-19.…”

“…The studies by Khoury et al 3 and Earle et al 4 take a first and important step toward a correlate of protection. The authors used data from published clinical studies of several vaccines against SARS-CoV-2 and evaluated the relationship between efficacy and neutralizing antibody titers.…”

“…The results from both teams showed a significant correlation between vaccine efficacy and vaccine-induced neutralizing antibody activity. Even titers of binding antibody (e.g., as measured by enzyme-linked immunosorbent assays, which are much easier to perform at large scale than neutralization assays are) seemed to correlate well with efficacy 4 . These findings suggest that antibodies may provide a correlate of protection, with further support for this coming from animal studies 12 and natural-infection cohorts 13 .…”

Reduced neutralizing activity of post-SARS-CoV-2 vaccination serum against variants B.1.617.2, B.1.351, B.1.1.7+E484K and a sub-variant of C.37

“…16 These changes may impact negatively on binding and neutralization by vaccine-induced antibodies, which are discussed as mechanistic correlates of protection. 17,18 It is, therefore, important to monitor neutralizing and binding activity of sera from vaccinees against these variants.…”

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

“…It comprises a highly variable S1 segment, which harbors the Nterminal domain (NTD) and the receptor-binding domain (RBD), and a more conserved S2 segment which includes the fusion peptide and heptad repeats required for virus fusion to host cells. Neutralizing antibody response is at present the best correlate of protection 1 . However, the adaptive immune response to SARS-CoV-2 infection is variable [2][3][4] .…”