Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial

Abstract

Antibody levels predict vaccine efficacy Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

“…Nonetheless, Gilbert et al demonstrated that the majority (68.5%) of vaccine efficacy is mediated by neutralizing antibody responses, with the remaining 31.5% of vaccine efficacy may be attributed to cell-mediated responses, other functional antibodies, and innate immunity. 16 These findings are in agreement with studies demonstrating the relationship between neutralizing antibody titers and breakthrough infections. 3,4…”

Booster of mRNA-1273 Strengthens SARS-CoV-2 Omicron Neutralization

“…Importantly, D614G was dominant over the period of time when the Moderna mRNA-1273 vaccine demonstrated 94% efficacy in preventing symptomatic COVID-19 in the Coronavirus Efficacy (COVE) phase 3 trial (2, 3), making D614G spike protein a primary reference standard. D614G spike binding and neutralizing antibodies also correlated with vaccine efficacy in the COVE study (4), further strengthening the utility of this spike as a reference standard. Notably, D614G is one of the most neutralization-sensitive forms of the virus known to date (5).…”

“…The Omicron variant that was first identified in South Africa in November 2021 is raising concerns because of its increased transmissibility and potential for reduced susceptibility to antibody neutralization attributed to the presence of a large number of spike mutations, including 15 mutations in the receptor binding domain (RBD) that is the major target for neutralizing antibodies (8, 9). To assess the potential risk of this variant to existing vaccines, identical serum samples from participants who received two standard inoculations of mRNA-1273 (100 µg) in the COVE study were tested for neutralization of Omicron in a lentivirus-based pseudovirus assay (4) in two independent laboratories: The Vaccine Research Center (VRC lab) in the National Institutes of Health (NIH), and Duke University Medical Center (Duke lab). One subset of samples from the COVE study was pre-selected as having high titers of neutralizing antibodies against D614G to enable detection of a wide range of titer reductions against Omicron.…”

Waning of SARS-CoV-2 Antibody levels response to inactivated cellular vaccine over 6 months among healthcare workers

“…Another report evaluated an immune correlate analysis of the mRNA-1273 COVID-19 vaccine trial and estimated a 90% vaccine efficacy of 57 RBD IgG level of 775 BAU/ml at the time. (12) In this view, even our seropositive HCW would not be protected against symptomatic infection at this moment.…”