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Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Multiple exposures to SARS-CoV-2 Spike enhance cross-reactive antibody-dependent cellular cytotoxicity against
Guillaume Beaudoin-Bussières1, Alexandra Tauzin1, Katrina Dionne1
1Centre de Recherche du CHUM, Montréal, QC, H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, H2X 0A9, Canada.
Abstract:
Vaccination or infection by SARS-CoV-2 elicits a protective immune response against severe outcomes. It has been reported that SARS-CoV-2 infection or vaccination elicits cross-reactive antibodies against other betacoronaviruses. While plasma neutralizing capacity was studied in great detail, their Fc-effector functions remain understudied. Here, we analyzed Spike recognition, neutralization and antibody-dependent cellular cytotoxicity (ADCC) against D614G, a recent Omicron subvariant of SARS-CoV-2 (JN.1) and SARS-CoV-1. Plasma from individuals before their first dose of mRNA vaccine, and following their second, third and sixth doses were analyzed. Despite poor neutralization activity observed after the second and third vaccine doses, ADCC was readily detected. By the sixth dose, individuals could neutralize and mediate ADCC against JN.1 and SARS-CoV-1. Since previous reports have shown that Fc-effector functions were associated with survival from acute infection, these results suggest that ADCC could help in combating future SARS-CoV-2 variants as well as closely related coronaviruses.
Insights
Antibody-dependent cellular cytotoxicity (ADCC) is induced by SARS-CoV-2 vaccination, offering protection against variants and related coronaviruses. This immune response complements neutralization, enhancing overall defense.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- SARS-CoV-2 infection and vaccination induce protective immunity, including cross-reactive antibodies against other betacoronaviruses.
- While neutralizing antibody capacity is well-studied, Fc-effector functions of antibodies remain less understood.
- Fc-effector functions, such as ADCC, are linked to survival during acute viral infections.
Purpose of the Study:
- To analyze Spike recognition, neutralization, and ADCC against SARS-CoV-2 variants (D614G, JN.1) and SARS-CoV-1.
- To evaluate the impact of mRNA vaccination (pre-vaccination, 2nd, 3rd, and 6th doses) on these immune responses.
- To investigate the potential role of ADCC in combating current and future coronavirus threats.
Main Methods:
- Analysis of plasma samples from individuals at various time points following mRNA SARS-CoV-2 vaccination.
- Measurement of Spike protein recognition, neutralizing antibody activity, and ADCC against different coronavirus strains.
- Comparison of immune responses elicited by vaccination across multiple doses.
Main Results:
- ADCC was detected after the second and third vaccine doses, despite limited neutralization activity.
- By the sixth vaccine dose, individuals exhibited both neutralization and ADCC against SARS-CoV-2 JN.1 and SARS-CoV-1.
- Antibody-dependent cellular cytotoxicity (ADCC) was readily detected even with poor neutralization after initial vaccine doses.
Conclusions:
- mRNA vaccination elicits robust ADCC responses against SARS-CoV-2 variants and SARS-CoV-1.
- ADCC represents a significant Fc-mediated immune response that complements neutralization.
- ADCC may play a crucial role in providing protection against current and future SARS-CoV-2 variants and related betacoronaviruses.
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