Application of M cell targeting ligand for oral vaccination to induce efficient systemic and mucosal immune responses against viral antigens

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 and animal farming industry. However, achieving effective antigen delivery into mucosal lymphoid organs and efficient immune stimulation are prerequisites to successful oral mucosal vaccine application. One promising approach for oral mucosal vaccine development is exploring the potential of M cells via M cell-targeting ligands which 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 pathogenic viral antigens, including envelope domain III (EDIII) of dengue virus (DENV) and VP1 of foot-and-mouth disease virus (FMDV) to provide the foundation for oral mucosal vaccine development against the pathogens. After oral administration of Co1-conjugated EDIII antigens, we observed efficient antigen delivery into Peyer's patch (PP). We also report the elicitation of EDIII-specific immunity in systemic and mucosal compartments by Co1 ligand (located in C-terminus of EDIII). Furthermore, the antibodies induced by the ligand-conjugated EDIII antigen showed effective virus neutralizing activity. We have confirmed the effects of M cell-targeting ligand to enhance antigen-specific immune activation by using VP1 of FMDV after oral administration of Co1-conjugated VP1. 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 antigens.