Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P6 and cholera toxin

Hotomi, Muneki; Saito, Tadahito; Yamanaka, Noboru

doi:10.1016/s0264-410x(98)00122-4

Cited by 45 publications

(31 citation statements)

References 27 publications

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“…Previous studies showed that specific antibodies induced by intranasal immunization were detected not only in nasal wash but also in saliva (18,26,38,43,44,46). Our previous study demonstrated that intranasal immunization is an effective regimen for the induction of antigen-specific mucosal IgA responses in the upper respiratory tract (26).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we established a method for isolating lymphocytes from the MEM and analyzed mucosal lymphocytes at the single cell level in the middle ear of normal mice. Results of that study showed that MEM has characteristics of a mucosal effector site (S. Suenaga, S. Kodama, S. Veyama, M. Suzuki, and G. Mogi, submitted for publication).Several studies concerning the prevention of OME by mucosal immunization have been reported, and these reports have suggested that intranasal immunization with P6 is effective for the prevention of OME (7,9,12,18,35). However, studies with mice have not investigated immune responses in the middle ear (18), and studies using chinchilla models have not analyzed immunological aspects (3,12,35).…”

mentioning

confidence: 99%

“…Several studies concerning the prevention of OME by mucosal immunization have been reported, and these reports have suggested that intranasal immunization with P6 is effective for the prevention of OME (7,9,12,18,35). However, studies with mice have not investigated immune responses in the middle ear (18), and studies using chinchilla models have not analyzed immunological aspects (3,12,35).…”

mentioning

confidence: 99%

“…However, studies with mice have not investigated immune responses in the middle ear (18), and studies using chinchilla models have not analyzed immunological aspects (3,12,35). In the present study, we investigated antigen-specific immune responses in the middle ear by intranasal immunization for the ultimate purpose of developing a mucosal vaccine for preventing OME.…”

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confidence: 99%

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Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media. One of the outer membrane proteins of NTHI, P6, is an antigen common to all strains and is considered as a candidate for mucosal vaccine. To elucidate the possibility of developing a nasal vaccine against nontypeable Haemophilus influenzae (NTHI) and to investigate mucosal immune responses in the middle ear, mice were immunized intranasally with the P6 outer membrane protein of NTHI, and P6-specific immune responses in the middle ear mucosa were examined. Mice were given with P6 and cholera toxin intranasally as an adjuvant on days 0, 7, and 14 and were killed on day 21. The P6-specific immunoglobulin A (IgA) antibody titer in ear wash was significantly elevated. Mononuclear cells were isolated from middle ear mucosa, and an increase in P6-specific IgA-producing cells was shown with an enzyme-linked immunospot assay. In addition, an increase in memory T cells in middle ear mucosa was detected with flow cytometric analysis after intranasal immunization. Moreover, in vitro stimulation with P6 resulted in proliferation of purified CD4 ؉ T cells from immunized mice, and these T cells expressed Th2 cytokine mRNA. These results indicate that P6-specific IgA-B-cell immune responses and selected Th2 cytokine expressing Th cells were induced in middle ear mucosa by intranasal immunization. These findings suggest that a nasal vaccine is useful for preventing otitis media with effusion.Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media with effusion (OME) and other upper respiratory tract diseases (10, 30). In patients with OME, this bacterium is frequently isolated from the nasopharynx, as well as from middle ear effusions, and the inhibition of NTHI colonization in the upper respiratory tract is considered effective in preventing OME. Due to the increase of antibiotic-resistant strains of NTHI in recent years, the development of a vaccine against this bacterium is considered an important goal for public health. Since NTHI lacks capsular antigens, the chief antigenicity is present in the outer membrane proteins (OMPs). One of the OMPs of NTHI, P6, is a common antigen to all strains and is considered as a candidate for mucosal vaccine (7,9,10,11,30,31).In the mucosal surface, secretory immunoglobulin A (IgA) plays a major role in protective immunity. We previously demonstrated that intranasal immunization was an effective regimen for inducing mucosal IgA immune responses in the upper respiratory tract (26) and that the nasal mucosal IgA immune responses induced by intranasal immunization were effective for the clearance of bacteria in the nasopharynx.The mucosal immune system is considered as a separate functional entity quite independent of the systemic immune system because the mucosal immune system possesses unique anatomic features and is composed of specialized subsets of lymphoid cells (21,27,34). Despite the recent emphasis on a better understanding of molecular and cellular aspects of the mucosal immune system,...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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“…ELISPOT was performed as previously described with modifications [20,24]. Multiscreen-IP plates (Millipore Corp., Billerica, MA) were pre-wetted with 35% ethanol, washed with PBS, and coated with either PA or BSA (Promega, Madison, WI) at 5 μg/ml, and incubated overnight at 4°C.…”

Section: Determination Of Antibody Forming Cells (Afcs) By Enzyme-linmentioning

confidence: 99%

Protection against anthrax by needle-free mucosal immunization with human anthrax vaccine

Zeng

Pichichero

2007

Vaccine

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Human vaccination with BioThrax™ requires six injections followed by annual boosters. This makes it difficult for the compliance of the immunization program and underscores the need for development of a new and optimized vaccination protocol. Current research aims to demonstrate the proof of concept to develop a needle free mucosal immunization protocol using a murine anthrax model. A/ J mice were immunized with BioThrax™ via an intranasal route. Sera, saliva, vaginal, and nasal washes were evaluated for protective antigen (PA) specific antibody responses by ELISA. Antigenspecific, antibody-secreting lymphocytes were measured by ELISPOT. Sera neutralization antibody titers were determined by in vitro anthrax lethal toxin (Letx) neutralization assay. Immunized animals were challenged by a lethal dose of Bacillus anthracis Sterne spores to determine the efficacy of the vaccination. Nasal mucosal immunization with BioThrax™ elicited robust serum and mucosal antibody responses against PA. The antigen specific antibodies neutralized anthrax Letx, as demonstrated by in vitro neutralization assays. Two doses of intranasal BioThrax™ were sufficient to completely protect A/J mice against challenge with 100×LD 50 Bacillus anthracis Sterne spores. The data suggests that intranasal administration may be an effective immunization modality for an improved immunization program against anthrax.

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Oral vaccines for preventing cholera

Sinclair

Abba

Zaman

et al. 2011

Cochrane Database of Systematic Reviews

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Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P6 and cholera toxin

Cited by 45 publications

References 27 publications

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Protection against anthrax by needle-free mucosal immunization with human anthrax vaccine

Oral vaccines for preventing cholera

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