Application of an M-cell-targeting ligand for oral vaccination induces efficient systemic and mucosal immune responses against a viral antigen

Abstract

Oral mucosal vaccination is an alternative method to overcome the pitfalls of current injection-based vaccines, such as pain and high cost of vaccination. It is a feasible and economic vaccine application, especially in developing countries. However, achieving effective antigen delivery into mucosal lymphoid organs and efficient immune stimulation are prerequisites to successful oral mucosal vaccination. One promising approach for oral mucosal vaccine development is exploring the potential of M cells via M-cell-targeting ligands that have the potential to deliver ligand-conjugated antigens into mucosal lymphoid organs and evoke conjugated-antigen-specific systemic and mucosal immune responses. Here, we investigated the M-cell-targeting ligand, Co1, in inducing specific immune responses against a pathogenic viral antigen, envelope domain III (EDIII) of dengue virus, to provide the foundation for oral mucosal vaccine development against the pathogen. After oral administration of Co1-conjugated EDIII antigens, we observed efficient antigen delivery into Peyer's patches. We also report the elicitation of EDIII-specific immunity in systemic and mucosal compartments by Co1 ligand (located in the C-terminus of EDIII). Furthermore, the antibodies induced by the ligand-conjugated EDIII antigen showed effective virus-neutralizing activity. The results of this study suggest that the M-cell-targeting strategy using Co1 ligand as a mucosal adjuvant may be applicable for developing oral vaccine candidates against pathogenic viral antigen.

Viral Immune Evasion in Dengue: Toward Evidence-Based Revisions of Clinical Practice Guidelines

“…Resulting antibodies induced by the ligand-conjugated EDIII antigen show effective virus- neutralizing activity. Taken together, these observations confirm that the M-cell-targeting strategy using Co1 ligand as a mucosal adjuvant may be a beneficial tool in the pursuit of effective vaccines for pathogenic DENV antigen [ 23 ].…”

Roles of M cells in infection and mucosal vaccines

“…Efficient antigen delivery into PPs was observed and the antibodies induced by the Co1-ligand-conjugated EDIII antigen showed effective virus-neutralizing activity. 65 Taken together, these results reveal that M-cell-targeting ligands with adjuvant activity can be designed to exploit our knowledge of receptors expressed on the apical surface of M cells involved in pathogen invasion.…”

“…[63][64][65] Co1 ligand promotes the uptake of fused antigen and enhances the immune response against the fused antigen, indicating that Co1 could be used as an adjuvant for targeted antigen delivery into the mucosal immune system to enhance immune induction. 64 Another promising approach used Co1 ligand to induce specific immune responses against a pathogenic viral antigen, EDIII of DENV.…”

Expression of the ATP-gated P2X7 Receptor on M Cells and Its Modulating Role in the Mucosal Immune Environment

“…In previous studies, it has been suggested that receptors expressed in the apical area of M cells could be utilized as M cell-targeting receptors for mucosal vaccine antigens ( 16 ). Consequently, we speculated that P2X 7 R might also serve as an M cell-targeting receptor for delivery of mucosal vaccine antigens.…”