Kinetics of the Antibody Response to Symptomatic SARS-CoV-2 Infection in Vaccinated and Unvaccinated Individuals in the Blinded Phase of the mRNA-1273 COVID-19 Vaccine Efficacy Trial

Abstract

Background Hybrid immunity is associated with more durable protection against COVID-19. We describe the antibody responses following SARS-CoV-2 infection in vaccinated and unvaccinated individuals. Methods The 55 vaccine-arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo-arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens [ancestral and variants of concern (VOC)] were assessed on Disease Day 1 (DD1) and 28 days later (DD29). Results The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine-group cases, there was a 1.88-fold rise in ancestral anti-spike bAbs one month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 anti-spike and anti-nucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs. placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group. Conclusions Following COVID-19, vaccinated participants had higher levels and breadth of anti-spike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.

Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration

“…To further investigate the effect of an anamnestic versus extant antibody response in protection, we evaluated the kinetics of antibody levels in vaccinated disease cases during the blinded phase of the COVE trial 30 . Fig.…”

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021–June 2022

“…This study demonstrated that patients with high anti-RBD bAb levels did not always have high anti-N levels. This observed difference could be due to differences in prior vaccination and infection history, as U.S.-licensed COVID-19 mRNA vaccines elicit anti-RBD but not anti-N antibodies [10, 11]; anti-N antibody responses to infection have been observed to differ among vaccinated versus unvaccinated persons [22] and non-neutralizing antibody mechanisms of protection mediated by anti-N bAb may be less affected by variants. We were unable to assess time from most recent SARS-CoV-2 infection for all patients; however, anti-N antibody levels may also reflect a shorter time interval between prior and current SARS-CoV-2 infection.…”

Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021—June 2022

“…Among vaccinated cases, lower baseline anti-RBD antibody concentrations among patients who had received 2 versus ≥3 mRNA vaccine doses were associated with greater antibody response but similar convalescent antibody concentrations. While anti-RBD bAb levels correlate with protection from infection with pre-Omicron variants [1, 3, 4], antibody levels measured against Omicron variants are greatly reduced [8, 14].…”

“…Because antibody levels measured during acute illness reflect an estimation of antibody levels close to the time of infection rather than response to current infection, comparison between antibody levels among case patients and SARS-CoV-2 uninfected patients may provide a measure of correlates of risk [15]. However, data, though limited, suggests that vaccination status and pre-existing neutralizing antibodies may affect anti-N antibody response by altering viral load in early illness [8, 16]. Measurement of immune response to infection and antibody levels after convalescence could improve understanding of vaccinated cases and hybrid immunity [17].…”

“…Elevated levels of anti-N antibody may indicate more recent SARS-CoV-2 infection [7]. As new SARS-CoV-2 variants have emerged, serologic assays that quantify IgG antibody binding to spike and nucleocapsid protein antigen have been used to evaluate humoral response to SARS-CoV-2 infection [8]. Post-infection antibodies may reduce risk of re-infection with new SARS-CoV-2 variants, suppress viral replication and reduce COVID-19 disease severity following re-infection [2,8].…”