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Review
. 2025 Feb 4;231(1):e1-e9.
doi: 10.1093/infdis/jiae464.

Unpredicted Protective Function of Fc-Mediated Inhibitory Antibodies for HIV and SARS-CoV-2 Vaccines

Li-Yun Lin  1   2 , Pierre Gantner  1   3 , Shuang Li  4   5 , Bin Su  4   5 , Christiane Moog  1   3   5   2
Affiliations
Review

Unpredicted Protective Function of Fc-Mediated Inhibitory Antibodies for HIV and SARS-CoV-2 Vaccines

Li-Yun Lin et al. J Infect Dis. .

Abstract

Developing effective vaccines is necessary in combating new virus pandemics. For human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the induction of neutralizing antibodies (NAb) is important for vaccine protection; however, the exact mechanisms underlying protection require further study. Recent data emphasize that even Abs that do not exhibit neutralizing activity may contribute to immune defense by Ab Fc-mediated inhibition. Abs exhibiting this function may counter virus mutations, which are acquired to escape from NAbs, and therefore broaden the protective Ab response induced by vaccination. The steps leading to inhibition are complex. How can these functions be measured in vitro? What inhibitory assay is physiologically relevant at mimicking effective in vivo protection? This review provides a comprehensive update on the current knowledge gaps on the Ab Fc-mediated functions involved in HIV and SARS-CoV-2 protection. Understanding the inhibitory effects of these Abs is vital for designing the next generation of protective HIV and SARS-CoV-2 vaccines.

Keywords: Fc-mediated immune response; HIV; SARS-CoV-2; neutralizing antibody; vaccine.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Fab and Fc domains of antibodies (Abs) involved in Ab functions. Neutralization and Fc-mediated inhibition by antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP).
Figure 2.
Figure 2.
Fc-mediated functions, ADCP and ADCC. Dual binding of antibody to Fc receptor and virus epitope leads either to the lysis of the infected target cell (ADCC) or the engulfment and digestion of the infected cell by phagocytosis (ADCP). Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; NK, natural killer cell.
See this image and copyright information in PMC

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MeSH terms