Nasal Vaccination with a Fusion Protein of Hemagglutinin A Antigenic Region and Maltose-Binding Protein Elicits CD4+ T Cell Responses via Toll-Like Receptor 4

• Published in: International Journal of Oral-Medical Sciences Vol. 10; no. 4; pp. 255 - 260
• Main Authors: Du, Yuan, Hashizume, Tomomi, Kurita-Ochiai, Tomoko, Abiko, Yoshimitsu, Ikeda, Takahiro, Tsurumi, Atsushi, Tomita, Naoya, Yamamoto, Masafumi
• Format: Journal Article
• Language: English
• Published: Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo 2012
• Subjects: 25k-hagA-MBP; Porphyromonas gingivalis; TLR4
• ISSN: 1347-9733; 2185-4254
• DOI: 10.5466/ijoms.10.255

Our previous study demonstrated that nasal immunization with the fusion protein of the 25-kDa antigenic hemagglutinin A antigenic region and maltose-binding protein (25k-hagA-MBP) elicited high levels of 25k-hagA-specific antibody responses in both systemic and oral mucosal areas. In this study, we further elucidated the immunogenicity of 25k-hagA-MBP using Toll-like receptor (TLR) 4 gene-deficient (TLR4-/-) mice. When CD4+ T cells isolated from the spleen and cervical lymph nodes (CLN) of 25k-hagA-MBP-stimulated TLR4+/+ mice were restimulated with 25k-hagA in vitro, significant proliferative responses were induced. In contrast, only low levels of CD4+ T cell proliferation were induced in restimulated cells isolated from TLR4-/- mice. Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP to TLR4+/+ mice produced significant levels of IL-6 and IL-10 in cells from the spleen and CLN. However, these cytokine responses were marginal in TLR4-/- mice nasally immunized with 25k-hagA-MBP. These results suggest that nasal immunization with 25k-hagA-MBP induces 25k-hagA-specific CD4+ T cells via a TLR4-dependent pathway.