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-␥), in the spleen and cervical lymph nodes (CLNs). Furthermore, increased numbers of CD11c؉ , 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.

Sublingual vaccination with fusion protein consisting of the functional domain of hemagglutinin A of Porphyromonas gingivalis and Escherichia coli maltose-binding protein elicits protective immunity in the oral cavity

“…These results are also in accordance with previous observations that sublingual immunization might favor the induction of both Th1‐type and Th2‐type responses (Cuburu et al ., ; Zhang et al ., ). In contrast, nasal vaccination with 25k‐hagA‐MBP exhibited Th2‐type responses owing to the predominant production of IL‐4 with no IFN‐γ (Du et al ., ). This discrepancy may indicate that the induction of Th1‐type and Th2‐type responses is determined by the route of the vaccine rather than the properties of the vaccine antigens.…”

“…Mice were orally infected with P. gingivalis as described previously (Du et al ., ), with minor modifications. Briefly, mice were given ad libitum access to ionized water containing sulfamethoxazole/trimethoprim (Sulfatrim; Goldline Laboratories, Fort Lauderdale, FL) at 10 mL per pint for 10 days.…”

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

“…MBP has been used as a chaperone component in vaccines to enhance antigen-specific humoral and cellular immune responses in immunized animals [ 2 , 3 , 4 , 5 , 6 , 7 ]. In addition to the immunostimulatory role, previous studies have also shown that MBP provides intrinsic maturation stimulus to DCs [ 7 ], induces Th1 cell activation, and increases the production of NO in mouse peritoneal macrophages [ 8 , 9 ].…”

“…When fused with a recombinant protein, MBP can increase the solubility of the fusion protein by a poorly understood mechanism, and thus is commonly used to improve the yield, facilitate the purification and enhance the stability of fusion proteins [ 2 , 3 ]. Recently, MBP has been used as a chaperone component in various vaccines against pathogenic bacteria and viruses to enhance the immunogenicity of recombinant protein-MBP fusion protein vaccines [ 4 , 5 , 6 ]. MBP has been shown to induce dendritic cell (DC) activation and production of proinflammatory cytokines [ 7 ].…”

Mucosal Vaccines for Dental Diseases

“…High salivary IgA antibodies to A. naeslundii, reduction in bone loss Crawford et al (1978) Purified fimbriae and fimbrial subunit from Porphyromonas gingivalis Parenteral immunization of rats Decreased bone loss; serum IgG, salivary IgA antibody Evans et al (1992b) Th2-type-specific T cell clone anti-Aggregatibacter actinomycetemcomitans Nasal immunization of mice Significant serum IgG, IgA, and salivary IgA anti-HagA antibody for at least 1 year; also significant reduction in alveolar bone loss for 1 year after immunization Du et al (2011) the design of vaccines for dental caries has been to select antigens that are of the most significance in the molecular pathogenesis of the disease. In the case of PD, antigen selection is more complex.…”