The following content is based on a study published in the Biomaterials Science Journal entitled “Preparation of glycopeptide-modified pH-sensitive liposomes for promoting antigen cross-presentation and induction of antigen-specific cellular immunity”.

Understanding the Immune System and Cross-Presentation

The human immune system, our body's complicated defense network, has two main tactics to tackle infections and illnesses. Humoral immunity is the creation of antibodies by B cells that bind to specific antigens on infections and mark them for destruction.

T cells, on the other hand, are responsible for cellular immunity because they either directly assault infected or malignant cells or coordinate the immune response by activating other immune cells.

Cross-presentation, an appealing process, improves the immune system's capacities even more. Antigen-presenting cells (APCs) can collect foreign antigens from outside the cell, digest them, and display them on their surface via MHC class I molecules.

This allows the immune system to recognize and respond to various dangers, such as viral infections and cancer, making cross-presentation an important strategy for effective immunological defense.

The Challenge of Delivering Antigens to the Cytosol

To elicit a strong immune response, antigens must be delivered to the proper location within the cell: the cytosol. This intracellular compartment contains the antigen processing machinery, which oversees breaking down the antigen into smaller pieces and displaying them on the cell surface.

However, delivering antigens directly to the cytosol presents a complicated task.

Traditional approaches, such as utilizing viral vectors or chemical transfection agents, can be ineffective and have serious adverse effects. These approaches may harm healthy cells, elicit undesired immunological responses, or have limited targeting capabilities.

As a result, there is an urgent need for novel techniques to safely and efficiently transfer antigens to the cytosol, maximizing their ability to elicit strong immune responses.

A Novel Approach to Delivering Antigens: Liposome-Based Delivery Systems

Scientists have devised a new technique to boost antigen delivery to immune cells, intending to increase the efficacy of vaccinations and immunotherapy. This method makes use of liposomes, which are tiny spherical vesicles made of lipids.

Key components of liposomes:

• Egg phosphatidylcholine is the fundamental structure of the liposome.
• The pH-responsive polysaccharide derivative allows the liposome to release its contents in the acidic cell environment, facilitating antigen transport to the cytosol.
• The soybean agglutinin-derived glycopeptide is a targeting molecule, leading liposomes to antigen-presenting cells (APCs) via sugar receptors on their surface.

To test their efficacy, these liposomes are loaded with the model antigen ovalbumin (OVA).

Researchers assessed several elements of these liposomes, including their ability to be taken up by cells, their efficacy in activating cross-presentation (the presentation of antigens to T cells), and their adjuvant capabilities. These factors were evaluated using both in vitro and in vivo experiments.

Fig. Demonstration of Immune Activation Pathway Using Antigen-Loaded Liposomes

This figure illustrates the immune activation pathway using antigen-loaded liposomes. Liposomes are absorbed by dendritic cells, which process and present the antigens on MHC Class I molecules.

This activates CD8+ T cells, leading to cytokine release and the proliferation of effector immune cells, enhancing the immune response for targeted therapies like vaccines and immunotherapy.

Promising Results: Improved Antigen Delivery and Immune Response

The researchers' innovative liposome-based delivery technology significantly improved antigen delivery and immune response. Liposomes treated with pH-responsive polysaccharides and glycopeptides were more efficiently absorbed by dendritic cells, which are essential antigen-presenting cells.

This increased cellular absorption resulted in greater cross-presentation of the model antigen, OVA, which is crucial for activating T lymphocytes.

Furthermore, the liposomes had high adjuvant capabilities, which stimulated the production of immune cells and inflammatory cytokines.

In vivo tests verified the success of this method, with liposomes administered subcutaneously inducing a robust antigen-specific cellular immune response and demonstrating therapeutic potential in tumor-bearing animals.

These findings demonstrate the delivery system's potential to revolutionize vaccination and immunotherapy development.

Conclusion

The revolutionary study on liposome-based antigen delivery systems has shown a promising pathway for cancer immunotherapy and infectious disease treatments. Scientists have considerably improved antigen transport to antigen-presenting cells by adding pH-responsive polysaccharides and glycopeptides into the liposome design.

This novel technique has resulted in enhanced cross-presentation, a critical step in activating T cells, which are an important component of the cellular immune response.

Furthermore, the liposomes exhibited strong adjuvant capabilities, prompting the immune system to produce a powerful response to the antigen.

In vivo tests confirmed the therapeutic potential of these liposomes. Liposomes administered subcutaneously to mice induced a high antigen-specific cellular immune response, resulting in considerable therapeutic effects in tumor-bearing animals.

These findings highlight the potential for this innovative delivery method to transform vaccination and immunotherapy development. These liposomes, by optimizing antigen delivery and increasing immune responses, offer hope for more effective treatments for a variety of disorders.

Reference

• Yuba E, Gupta RK. Preparation of glycopeptide-modified pH-sensitive liposomes for promoting antigen cross-presentation and induction of antigen-specific cellular immunity. Biomaterials Science. 2024;12(6):1490-501.
• Janeway Jr CA, Travers P, Walport M, Shlomchik MJ. Principles of innate and adaptive immunity. In Immunobiology: The Immune System in Health and Disease. 5th edition 2001. Garland Science.
• Woodle MC, Papahadjopoulos D. [9] Liposome preparation and size characterization. Methods in Enzymology. 1989 Jan 1;171:193-217.
• Reddy S, Etikala A. Liposomes–a novel drug delivery system: A review. Int J Pharm Biol Sci. 2019;18(2):704-15.

Blog Authors

Sradha A S, Sinchana Hegde, Tarannum Tamboli, Kaveri Sonawane, Shreepratha Thakkar, Eiji Yuba and Rajesh Kumar Gupta*

Protein Biochemistry Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune

*E-mail: rajeshkumar.gupta@dpu.edu.in

Frequently Asked Questions

Q1. What is the main goal of liposome-based antigen delivery?

To enhance antigen transport to immune cells for a stronger immune response.

Q2. Why is cross-presentation important?

It helps activate T cells by displaying antigens on MHC class I molecules.

Q3. What role do pH-responsive polysaccharides play in liposomes?

They help release the antigen in the acidic environment inside cells.

Q4. Why is ovalbumin (OVA) used in the study?

It serves as a standard model antigen to evaluate delivery efficiency.

Q5. How do glycopeptides improve liposome performance?

They help target the liposomes to antigen-presenting cells.

Q6. What cells mainly absorb these liposomes?

Dendritic cells, which are key antigen-presenting cells.

Q7. What immune cells are activated through cross-presentation?

CD8+ T cells responsible for cellular immunity.

Q8. How were the liposomes tested?

Through both in vitro and in vivo experiments.

Q9. What therapeutic potential was shown in animal studies?

Significant antigen-specific immune response and tumor reduction.

Q10. Can this liposome system improve vaccines?

Yes, by improving antigen delivery and boosting immune activation.