ADCC in Virus Disease

ADCC & Immune system

The immune system helps us fight off the invasion of bacteria and viruses. When immunity is weakened, the body is prone to symptoms, such as infection. Due to weakened immunity, the immune system is unable to destroy pathogenic microorganisms normally, resulting in infections that are difficult to heal on their own.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important defense mechanism used by the immune system to fight viral infections. ADCC is generally mediated by natural killer cells (NK), and sometimes neutrophils and eosinophils. Here, the antibody binds to an antigen on the surface of the target cell and then binds to the Fc receptor on the surface of a natural killer cell (NK) cell or macrophage. NK cells or macrophages are then able to release cytotoxins from the cells to kill the target cells.

Fig.1 Mechanism of action of monoclonal antibodies in viral infection. ¹

Antiviral Antibody

Antibodies are natural biomolecules produced by plasma cells or memory B cells after infection with pathogens or vaccinations to fight viral infections through a variety of mechanisms. It prevents the viral glycoprotein from binding to the target host cell with the protein coat of the virus. The main functions of these proteins in the viral life cycle are: binding to cell receptors, mediating the fusion of viruses with cell membranes, or infiltrating into the cytoplasm.

In addition, antibody effector function mediated by binding to complement proteins C1q or FcγR on leukocytes may also be involved in the fight against viral infection. Antibody-activated complement directly lyses viral or infected host cells, promotes or induces phagocytosis, or triggers the release of toxic chemicals such as cytokines or reactive oxygen species.

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Fig.2 Antibody development process. ¹

Antibody Engineering to Enhance ADCC

Several regions of the mAb can be modified to improve its therapeutic properties. In addition to isotype-induced variants, several combinatorial mutations in the Fc domain have been shown to increase or decrease ADCC/CDC effects. For example, House et al.² investigated the ability of mAb combination therapies to specifically neutralize SARS-CoV-2. The effects of two mutations (YTE and LALA) on Fc effector function and the ability to mitigate potential antibody-dependent disease enhancement were investigated by mutating the Fc domain.

The following is the latest research on ADCC in the field of different types of viral infections:

• ADCC in HIV-1 Disease
• ADCC in SARS-CoV-2 Disease
• ADCC in Influenza Virus Disease
• ADCC in Herpes Simplex Virus Disease
• ADCC in Simian Immunodeficiency Virus Disease
• ADCC in Hepatitis C Virus Disease
• ADCC in Zika Virus Disease

References

1. Pantaleo, G.; et al. "Antibodies to combat viral infections: development strategies and progress." Nat Rev Drug Discov. (2022) 21, 676–696.
2. House, R.V.; et al. "Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics." PloS one. (2022) 17,6 e0267796.