N-Glycosylation of Antibodies: Biological Effects in Infections and Therapeutic Applications

This article systematically summarizes the role of antibody N-glycosylation in infections and vaccine responses, as well as its impact on effector functions, complement activation, and pathogen neutralization, making it of significant translational application value.

 

Literature Overview

This article, titled "Biological Effects of Antibody N-Glycosylation During Infections and Therapeutic Applications," published in the journal Antibodies, reviews and summarizes the role of antibody N-glycosylation in immune responses, particularly its dynamic changes in infectious diseases and vaccine-induced immunity. The article also explores N-glycosylation modifications across different antibody classes (IgG, IgA, IgM, IgE) and their influence on antibody functions such as ADCC, complement activation, and pathogen neutralization. Moreover, it highlights that the N-glycosylation profile can be used to assess infection stages and severity and plays a critical role in the pharmacokinetics and safety of therapeutic monoclonal antibodies.

Background Knowledge

Antibodies are key effector molecules of the adaptive immune system, recognizing antigens through their Fab fragment, while their Fc fragment engages in effector functions through interactions with Fc receptors or the complement system. N-glycosylation is a crucial post-translational modification of antibodies, primarily occurring at asparagine 297 (Asn297) in the Fc region, affecting antibody structure, stability, and interaction with effector molecules. During infections or vaccine responses, the N-glycosylation profile of antibodies can undergo dynamic changes, such as low fucosylation, high sialylation, or galactosylation, which can influence the magnitude and type of antibody-mediated immune responses. For instance, glycosylation modifications of antibodies have been found to correlate with disease severity in infections like SARS-CoV-2, tuberculosis, influenza, and dengue, while specific glycosylation patterns can change after vaccination. Additionally, N-glycosylation significantly affects therapeutic antibody characteristics, including half-life, effector functions, and safety. These findings provide new molecular mechanisms and potential biomarkers for immune regulation in infections, vaccine development, and monoclonal antibody therapies.

 

 

Research Methods and Experiments

The article systematically reviews the N-glycosylation sites of IgG, IgA, IgM, IgD, and IgE antibodies and their functional implications. For example, IgG N-glycosylation predominantly occurs at the Asn297 residue within the Fc region, while certain IgG3 subclasses can also be glycosylated at Asn392. By analyzing various infection models (e.g., tuberculosis, SARS-CoV-2, HIV, dengue) and vaccine response models, the authors summarize the dynamic changes in N-glycosylation profiles during disease progression and discuss how these modifications influence antibody functions such as ADCC, complement activation, and pathogen neutralization. Furthermore, the article evaluates the regulatory role of N-glycosylation in the pharmacokinetics and safety of monoclonal antibodies.

Key Conclusions and Perspectives

• N-glycosylation of IgG antibodies undergoes dynamic changes during infections or vaccine responses. For instance, low fucosylation enhances FcγRIII binding and promotes ADCC, whereas high sialylation reduces inflammatory responses and supports immune tolerance.
• The N-glycosylation of IgA antibodies affects their interaction with FcαR1, and the level of sialylation correlates with IgA-mediated pro-inflammatory or anti-inflammatory effects.
• IgM glycosylation modifications can influence its interaction with B cell receptors and complement activation capacity, exhibiting distinct modification patterns during infections such as SARS-CoV-2.
• In diseases like tuberculosis and viral infections (e.g., HIV, SARS-CoV-2), antibody N-glycosylation profiles may serve as potential biomarkers for infection stage and severity.
• Following vaccination, specific changes in antibody N-glycosylation profiles occur, such as increased sialylation and fucosylation, which influence antibody effector functions.
• N-glycosylation significantly affects the pharmacokinetics and therapeutic safety of antibodies. For example, low-fucosylated mAbs may exhibit enhanced effector cell activation but could also increase inflammatory responses.

Research Significance and Prospects

The dynamic regulation of antibody N-glycosylation profiles provides new molecular insights into infection immunology and vaccine research, and also offers a theoretical basis for optimizing monoclonal antibody therapies. Future studies could further explore how glycosylation modifications influence individual variability in immune responses and whether therapeutic antibody functions can be optimized by modulating glycosyltransferase activity. In addition, investigating the immunomodulatory and pathological effects of antibody glycosylation changes using animal or cellular models could aid in the development of more effective immunotherapeutic strategies.

 

 

Conclusion

This article comprehensively reviews the roles of antibody N-glycosylation in infections and therapeutic contexts, highlighting its significance in immune effector functions, complement activation, pathogen neutralization, and vaccine-induced immunity. Glycosylation modifications of antibodies such as IgG, IgA, IgM, etc., are class-specific and exhibit variable patterns under different infections or immune stimuli, potentially reflecting disease stages or immune status. These findings deepen our understanding of antibody functional regulation mechanisms and provide new biomarkers and intervention targets for monoclonal antibody engineering and vaccine development. Looking ahead, modulating glycosyltransferases (e.g., FUT8, ST6GAL1, GnT-III) may offer a strategy to optimize therapeutic antibody activity and safety, thereby enhancing their application in oncology, autoimmune diseases, and infectious disease treatment.

 

Jessica Castañeda-Casimiro, Luis Vallejo-Castillo, Eliud S Peregrino, Isabel Wong-Baeza, and Jeanet Serafín-López. N-Glycosylation of Antibodies: Biological Effects During Infections and Therapeutic Applications. Antibodies.