Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

Abstract

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2-neutralization, with these ‘elite neutralizers’ also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity and gender as key factors predicting SARS-CoV-2 neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a stable long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.

Anti-spike antibody response to natural SARS-CoV-2 infection in the general population

“…after mild disease 20,27 mount a lower antibody response that wanes more slowly, whilst others, produce higher antibody responses but that wane more quickly. This contrasts with a previous healthcare worker study which found a positive correlation between IgG half-life and peak levels 15 , but agrees with a study on 963 infected individuals reporting a faster decay of IgG in hospitalized patients with high initial response than individuals with asymptomatic or mild infections 23 . Since most SARS-CoV-2 infection is mild/asymptomatic, the duration of antibody responses in our study are likely to best generalise to the population at large.…”

“…These participants showed classical responses, with rises in antibody levels over the 4-5 weeks following their first PCRpositive sample, followed by subsequent waning. Class 1 had lower Ct values (median [IQR] 22 [17][18][19][20][21][22][23][24][25][26][27][28], p<0.001 vs. any other class), and a higher percentage of reported symptoms (77.7%, p<0.001 vs. any other class) and classic symptoms (54.8%, p<0.001 vs. any other class). Class 1 also had a lower percentage of single gene positives (5.2%, p<0.001 vs. any other class).…”

“…Estimates for the half-life of anti-spike IgG antibodies (associated with neutralising activity 16 ) vary from 36 to 244 days 15,[17][18][19][20][21][22][23] . Similarly anti-nucleocapsid IgG half-lives have been estimated between 35 and 85 days 15,19,20,22 .…”

“…Among those who do seroconvert, data on the trajectory and duration of antibody responses to different SARS-CoV-2 antigens vary, partly reflecting assay-dependent differences even where similar viral antigens are studied 14,15 , as well as differences in the populations and disease groups investigated. Estimates for the half-life of anti-spike IgG antibodies (associated with neutralising activity 16 ) vary from 36 to 244 days 15,17–23 . Similarly anti-nucleocapsid IgG half-lives have been estimated between 35 and 85 days 15,19,20,22 .…”

Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

“…As these results highlight DZIF-10c as a very potent S-binding antibody, we further characterized its neutralizing properties. The in vitro neutralizing activity of DZIF-10c was first evaluated against a panel of six pseudovirus variants [ 33 , 34 ]. DZIF-10c demonstrated potent neutralizing activity against all SARS-CoV-2 S variants tested, including a variant carrying the D614G mutation, with an average IC 50 of 0.007 µg/mL ( Figure 1 B).…”