Riboflavin as a Mucosal Adjuvant for Nasal Influenza Vaccine.

Yinyan Yin,Bangyue Zhou,Xing Xu,Daxin Peng,Sujuan Chen,Tao Qin,Jinyuan Wang

doi:10.3390/vaccines9111296

Abstract

Intranasal immunization with whole inactivated virus (WIV) is an important strategy used for influenza prevention and control. However, a powerful mucosal adjuvant is required to improve nasal vaccine efficacy. Riboflavin, as a food additive with the advantages of being safe and low-cost, widely exists in living organisms. In this paper, the mucosal adjuvant function of riboflavin was studied. After intranasal immunization with H1N1 WIV plus riboflavin in mice, we found that the mucosal immunity based on the secretory IgA (sIgA) levels in the nasal cavity, trachea, and lung were strongly enhanced compared with H1N1 WIV alone. Meanwhile, the IgG, IgG1, and IgG2a levels in serum also showed a high upregulation and a decreased ratio of IgG1/IgG2a, which implied a bias in the cellular immune response. Moreover, riboflavin strongly improved the protection level of H1N1 inactivated vaccine from a lethal influenza challenge. Furthermore, riboflavin was found to possess the capacity to induce dendritic cell (DC) phenotypic (MHCII, CD40, CD80, and CD86) and functional maturation, including cytokine secretion (TNF-α, IL-1β, IL-12p70, and IL-10) and the proliferation of allogeneic T cells. Lastly, we found that the DC maturation induced by riboflavin was dependent on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which plays an important role in immune regulation. Therefore, riboflavin is expected to be developed as an alternative mucosal adjuvant for influenza nasal vaccine application.

Highlights

Influenza is a highly infectious zoonosis that can cause human and animal death [1].In 1918, a deadly influenza pandemic caused by the H1N1 influenza virus infected approximately 500 million people and resulted in 50 to 100 million people dying worldwide [2].In 2009, a new H1N1 subtype influenza virus spread rapidly worldwide among humans and caused approximately 18,500 worldwide deaths for the period of April 2009 to August2010 [3]
We found that riboflavin (10–80 μM) significantly stimulated the proliferation of splenic lymphocytes compared with the control, implying that riboflavin has the ability to activate the host immune response and might be developed as a potential vaccine adjuvant (Figure S1, Supplementary Materials)
We did not find cytotoxicity of riboflavin (≤80 μM) in dendritic cell (DC) (Figure 1C), which act as antigen-presenting cells (APCs) to trigger a downstream series of immune responses [21]

Summary

Introduction

Influenza is a highly infectious zoonosis that can cause human and animal death [1].In 1918, a deadly influenza pandemic caused by the H1N1 influenza virus infected approximately 500 million people and resulted in 50 to 100 million people dying worldwide [2].In 2009, a new H1N1 subtype influenza virus spread rapidly worldwide among humans and caused approximately 18,500 worldwide deaths for the period of April 2009 to August2010 [3]. Influenza is a highly infectious zoonosis that can cause human and animal death [1]. In 1918, a deadly influenza pandemic caused by the H1N1 influenza virus infected approximately 500 million people and resulted in 50 to 100 million people dying worldwide [2]. In 2009, a new H1N1 subtype influenza virus spread rapidly worldwide among humans and caused approximately 18,500 worldwide deaths for the period of April 2009 to August. It is known that the nasal cavity is the primary entry site of influenza virus. If mucosal immune protection is established in the nasal mucosa, early viral infection and shedding will be cut off due to the secretory IgA (sIgA) antibody at the mucosal site [4,5]. Inactivated influenza vaccines with a good level of safety are widely

Methods

Results

Conclusion