Nasal immunization with a fusion protein consisting of the hemagglutinin A antigenic region and the maltose-binding protein elicits CD11c(+) CD8(+) dendritic cells for induced long-term protective immunity.

Abstract

We assessed the efficacy of a fusion protein consisting of the 25-kDa antigenic region of Porphyromonas gingivalis hemagglutinin A and the Escherichia coli maltose-binding protein (25k-hagA-MBP) as a nasal vaccine for the prevention of oral infection with P. gingivalis. Nasal immunization with 25k-hagA-MBP induced high levels of 25k-hagA-specific serum IgG, serum IgA, and salivary IgA antibodies in a Toll-like receptor 4 (TLR4)-dependent manner. These antibody responses were maintained for at least 1 year after immunization. Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP induced antigen-specific CD4(+) T cells producing interleukin 4 (IL-4) and IL-5, but not gamma interferon (IFN-γ), in the spleen and cervical lymph nodes (CLNs). Furthermore, increased numbers of CD11c(+) CD8α(+), but not CD11c(+) CD11b(+) or CD11c(+) B220(+), dendritic cells with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) molecules were noted in the spleen, CLNs, and nasopharynx-associated lymphoreticular tissues (NALT). Interestingly, when 25k-hagA-MBP or cholera toxin (CT) was given intranasally to enable examination of their presence in neuronal tissues, the amounts of 25k-hagA-MBP were significantly lower than those of CT. Importantly, mice given 25k-hagA-MBP nasally showed a significant reduction in alveolar bone loss caused by oral infection with P. gingivalis, even 1 year after the immunization. These results suggest that 25k-hagA-MBP administered nasally would be an effective and safe mucosal vaccine against P. gingivalis infection and may be an important tool for the prevention of chronic periodontitis in humans.

• Authors: Yuan Du, Tomomi Hashizume, Tomoko Kurita-Ochiai, Satoshi Yuzawa, Yoshimitsu Abiko, Masafumi Yamamoto
• Journal: Infection and immunity (Infect Immun) Vol. 79 Issue 2 Pg. 895-904 (Feb 2011) ISSN: 1098-5522 [Electronic] United States
• PMID: 21115722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, Bacterial
• Bacterial Proteins
• Bacterial Vaccines
• CD11c Antigen
• CD8 Antigens
• Lectins
• Maltose-Binding Proteins
• Recombinant Fusion Proteins
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• hemagglutinin A, Porphyromonas gingivalis

Topics

• Adjuvants, Immunologic
• Administration, Intranasal
• Alveolar Bone Loss (prevention & control)
• Animals
• Antigens, Bacterial
• Bacterial Proteins (chemistry, immunology)
• Bacterial Vaccines (administration & dosage, immunology)
• Bacteroidaceae Infections (prevention & control)
• CD11c Antigen (immunology)
• CD8 Antigens (immunology)
• Dendritic Cells (immunology)
• Gene Expression Regulation (immunology)
• Lectins (chemistry, immunology)
• Maltose-Binding Proteins (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Porphyromonas gingivalis (immunology, metabolism)
• Recombinant Fusion Proteins (administration & dosage, immunology)
• Toll-Like Receptor 4 (genetics, metabolism)