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.

Virology
|March 27, 2025
PubMed

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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