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

Abstract

This study demonstrated that sublingual immunization with a fusion protein, 25k‐hagA‐MBP, which consists of a 25‐kDa antigenic region of hemagglutinin A purified from Porphyromonas gingivalis fused to maltose‐binding protein (MBP) originating from Escherichia coli as an adjuvant, elicited protective immune responses. Immunization with 25k‐hagA‐MBP induced high levels of antigen‐specific serum IgG and IgA, as well as salivary IgA. High level titers of serum IgG and IgA were also induced for almost 1 year. In an IgG subclass analysis, sublingual immunization with 25k‐hagA‐MBP induced both IgG1 and IgG2b antibody responses. Additionally, numerous antigen‐specific IgA antibody‐forming cells were detected from the salivary gland 7 days after the final immunization. Mononuclear cells isolated from submandibular lymph nodes (SMLs) showed significant levels of proliferation upon restimulation with 25k‐hagA‐MBP. An analysis of cytokine responses showed that antigen‐specific mononuclear cells isolated from SMLs produced significantly high levels of IL‐4, IFN‐γ, and TGF‐β. These results indicate that sublingual immunization with 25k‐hagA‐MBP induces efficient protective immunity against P. gingivalis infection in the oral cavity via Th1‐type and Th2‐type cytokine production.

Immunization with a MOMP-Based Vaccine Protects Mice against a Pulmonary Chlamydia Challenge and Identifies a Disconnection between Infection and Pathology

“…However, MBP can also acts as an adjuvant [44]–[48]. Proteins fused with MBP elicit significantly more serum antibodies than untagged proteins [45]–[47], as MBP is a TLR4 agonist that stimulates cytokine production and expression of co-stimulatory molecules on DCs [44]. This provides an explanation for why IN immunization with recombinant MOMP, in the absence of an adjuvant, elicits a strong antigen-specific response as opposed to mucosal tolerance [49], [50].…”

Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease

“…gingivalis infection, mice were sacrificed and gingival tissues from the upper and lower jaws were carefully removed using microsurgical tweezers under a stereomicroscope. Cells from gingival tissues were prepared by gently teasing the tissue through sterile stainless steel screens, followed by an enzymatic dissociation procedure with 0.3 mg/mL of collagenase (Nitta Gelatin Co. Ltd., Osaka, Japan) in RPMI 1640 (Wako Pure Chemical Industries Ltd., Osaka, Japan) 40 . GMCs were enriched to 60–80% purity through discontinuous Percoll gradients (Pharmacia Fine Chemicals, Uppsala, Sweden) and resuspended in RPMI 1640 supplemented with HEPES buffer (15 mM), L-glutamine (2 mM), penicillin (100 U/mL), streptomycin (100 μg/mL), and 10% fetal bovine serum (Biofill, Victoria, Australia) (complete medium).…”

Mucosal Vaccination Against Periodontal Disease: Current Status and Opportunities

“…Most PD vaccines targeted Porphyromonas gingivalis, while a few targeted Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, or Eikenella corrodens. All studies found significant increases in antigen-specific antibodies, and those assessing clinical effects also observed reduced pathological manifestations (91,(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115). While these data are encouraging, it should be noted that all but two studies (113,116) used rodents, which have limited translational values.…”

“…Indeed, all eleven preclinical studies that evaluated this reported more dual immunity in the oral cavity after mucosal vaccination compared to systemic vaccination (89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99). Furthermore, several studies reported protection against experimental PD-associated bone loss or gingival swelling/ abscessation by mucosal immunization (91,(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115). While these data support the rationale for mucosal PD vaccines, it must be noted that all but two of these studies used rodent PD models (113,116).…”