Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
Highlights
Control of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic relies on population resistance to infection due to a postinfection and vaccination-induced immunity
SARS-CoV-2 antibodies were assessed in reverse transcription polymerase chain reaction (RT-PCR)–confirmed COVID-19 convalescent adults in 2 Australian cohorts: Adapting to Pandemic Threats (ADAPT), a hospital-based cohort of patients recruited during the first and second wave of infection in Australia (n = 83 and n = 17), and Australian Red Cross Lifeblood cohort (LIFE), a cohort of plasma donors (n = 159) (Table 1, Fig 1A)
Antibody immunoreactivity to SARS-CoV-2 antigens, inhibition of virus–cell fusion, live SARS-CoV-2 neutralization, and immunoreactivity to Spike emerging variants were assessed, and antibody features were compared with demographic data (Fig 1A)
Summary
Control of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic relies on population resistance to infection due to a postinfection and vaccination-induced immunity. Current questions relate to the level, breadth, and longevity of generated immunity and whether mutation of the virus will compromise immunity. Previous studies reported varying results in longitudinal changes of the virus-specific antibody response. Some detected stable antibody titers 4 to 6 months after diagnosis [1,2], while others reported waning of the antibody response 2 to 3 months after infection [3,4]. Differences in assay sensitivity and antigen targets may account for these discrepancies, with Spike and Nucleocapsid being the main antigens investigated. Immunoreactivity to other abundant antigens, such as Membrane or Envelope, is unknown
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