Effects of Oral and Systemic Immunization on Nasopharyngeal Clearance of Nontypeable <i>Haemophilus influenzae</i> in BALB/c Mice

Kurono, Yuichi; Shigemi, Hideo; Kodama, Satoru; Mogi, Goro

doi:10.1097/00005537-199605000-00018

Cited by 18 publications

(19 citation statements)

References 18 publications

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“…Several models have been useful in evaluating vaccine antigens for nontypeable H. influenzae. These include the chinchilla model of otitis media (21, 76, 114) and various pulmonary and nasopharyngeal clearance models in the mouse and rat (130,144,166,167,204,335,352). The ability of an antigen to generate a protective immune response in an animal model is used as a rationale to proceed with further testing of a potential vaccine antigen.…”

Section: Immune Response (I) Interpreting the Literature Human Antimentioning

confidence: 99%

Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review

2001

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SUMMARY Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. The precise role of bacterial infection in the course and pathogenesis of COPD has been a source of controversy for decades. Chronic bacterial colonization of the lower airways contributes to airway inflammation; more research is needed to test the hypothesis that this bacterial colonization accelerates the progressive decline in lung function seen in COPD (the vicious circle hypothesis). The course of COPD is characterized by intermittent exacerbations of the disease. Studies of samples obtained by bronchoscopy with the protected specimen brush, analysis of the human immune response with appropriate immunoassays, and antibiotic trials reveal that approximately half of exacerbations are caused by bacteria. Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most common causes of exacerbations, while Chlamydia pneumoniae causes a small proportion. The role of Haemophilus parainfluenzae and gram-negative bacilli remains to be established. Recent progress in studies of the molecular mechanisms of pathogenesis of infection in the human respiratory tract and in vaccine development guided by such studies promises to lead to novel ways to treat and prevent bacterial infections in COPD.

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Section: Immune Response (I) Interpreting the Literature Human Antimentioning

confidence: 99%

Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review

2001

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“…Enhanced clearance of NTHi from the middle ear was observed in chinchillas after systemic immunization with a mixture of outer membrane proteins, and the protection was associated with antigen-specific bactericidal antibodies (1,2,16). Enhanced NTHi clearance from the mucosal surface generally correlates well with antigen-specific mucosal IgA titer but not with serum IgA and IgG antibody levels after mucosal immunization (24). The present study showed that intranasal immunization with P6 and CT effectively enhanced the clearance of NTHi from the murine middle ear.…”

Section: Discussionmentioning

confidence: 47%

“…Suspensions were centrifuged, an aliquot from each supernatant was serially diluted 10-fold, and 10-l aliquots of the diluted samples were spread on chocolate agar plates to determine the concentration of live bacteria. After overnight incubation at 37°C in 5% CO 2 , NTHi was identified by standard bacteriologic techniques, including Gram staining and determination of their V and X growth factor requirements, and the colonies were counted (24). The concentration of NTHi was expressed as CFU per milliliter of ear wash.…”

Section: Methodsmentioning

confidence: 99%

Intranasal Immunization Enhances Clearance of NontypeableHaemophilus influenzaeand Reduces Stimulation of Tumor Necrosis Factor Alpha Production in the Murine Model of Otitis Media

et al. 2001

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Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media (OM). One of the outer membrane proteins of NTHi, P6, is a common antigen to all strains and is considered a candidate for mucosal vaccine. We have previously reported that intranasal immunization with P6 and cholera toxin (CT) could induce P6-specific immunoglobulin A (IgA) antibodies in the middle ear. In the present study, we assessed the effect of intranasal immunization for the protection against NTHi-induced OM. Mice were immunized intranasally with P6 and CT as an adjuvant on days 0, 7, and 14. Control mice were given phosphate-buffered saline (PBS) without antigen. One week after the final immunization, a suspension of live NTHi (10 7 CFU) was injected into the tympanic cavity to induce experimental OM. On days 3 and 7 after bacterial challenge, mice were killed and middle ear effusions (MEEs) were collected. All immunized mice showed elevated titers of P6-specific antibodies in MEEs. The rank order of specific antibody included, from highest to lowest levels, IgG, IgA, and IgM. In addition, immunized mice showed enhanced clearance of NTHi from the middle ear and the number of NTHi in MEEs of immunized mice was reduced by 97% on day 3 and by 92% on day 7 after bacterial challenge relative the number in the MEEs of control mice. The protective effect of intranasal immunization on the incidence of NTHi-induced experimental OM was evident on day 7 after challenge. By day 7, the number of MEEs in immunized mice was 64% less than that in control mice and the incidence of NTHi culture-positive MEEs in immunized mice was 56% less than that in control mice. Less stimulation of tumor necrosis factor alpha (TNF-␣) production in the middle ear was evident on day 3 after challenge. Immunized mice showed lower concentrations of TNF-␣ in MEEs. These results indicate that intranasal immunization affords protection against experimental OM as evidenced by enhanced clearance of NTHi and less stimulation of TNF-␣ production in the middle ear. These findings suggest that a nasal vaccine might be useful for preventing OM.Otitis media (OM) is one of the most common infectious diseases in children, and the peak incidence of this disease occurs in early childhood. Nontypeable Haemophilus influenzae (NTHi) is a major causative pathogen of OM and is often isolated from middle ear effusions (MEEs) and the nasopharynx (12). Because of the increased incidence of antibioticresistant strains of NTHi in recent years, the development of a vaccine against this bacterium is considered an important goal for public health (14, 15). Recent efforts to develop an effective vaccine candidate against NTHi have focused on P6, an outer membrane protein of NTHi and a common antigen to all strains (32, 33).The middle ear mucosa is capable of producing local and systemic responses after an appropriate antigenic stimulus (30). Local immunity in the middle ear, in conjunction with systemic immunity, plays an important role in OM. Antigenspecific antibodies appear in MEE ...

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“…These B cells are found in the tonsils and adenoids. Further support for the concept of a common mucosal immune system playing a role in the development of inflammation in the middle ear has been reported by Kurono et al [15] in Japan. Enhancement of mucosal IgA responses in the middle ear cavity against NTHi follows oral immunization with these bacteria [15].…”

Section: Lymphocyte Trafficking In the Middle Ear In Otitis Mediamentioning

confidence: 59%

“…Kurono et al [15] 1994 Both specific and nonspecific homing of lymphocytes from GALT and peripheral lymphoid tissue. Bernstein et al [14] 1988…”

Section: Investigatorsmentioning

confidence: 99%

Immunologic aspects of otitis media

Bernstein

2002

Curr Allergy Asthma Rep

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The middle ear cleft is a modified gas pocket which functions normally when the gas contents are regulated by a normal eustachian tube, resulting in equalization of middle ear pressure to that of the environment. The most important regulator of this middle ear pressure is the eustachian tube, a critical passageway from the nasopharynx into the middle ear. Any alteration of eustachian tube mucociliary function caused by virus, allergy, pollutants, or alteration of the normal homeostasis of the nasopharynx will result in eustachian tube obstruction. This, in turn, leads to underventilation of the middle ear, and transudation of fluid. If bacteria or virus or viral-bacterial interaction leads to infectious disease of the middle ear, an immune response is produced as a result of the inflammatory response, allowing lymphocytes and antigen-presenting cells to enter into the middle-ear mucosa. This article summarizes the immunologic reactivity in the middle ear following a viral-bacterial inflammatory reaction in the middle-ear mucosa. Although secretory IgA is critical for protection of the nasopharynx, its function in the middle ear has still not been resolved. The evidence strongly suggests that IgG1 and IgG3 subclasses are responsible for eradication of middle ear pathogens. Finally, a review of alternative approaches to the prevention of otitis media is briefly discussed in this critical period of emergence of resistant bacteria to available antibiotics.

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Effects of Oral and Systemic Immunization on Nasopharyngeal Clearance of Nontypeable Haemophilus influenzae in BALB/c Mice

Cited by 18 publications

References 18 publications

Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review

Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review

Intranasal Immunization Enhances Clearance of NontypeableHaemophilus influenzaeand Reduces Stimulation of Tumor Necrosis Factor Alpha Production in the Murine Model of Otitis Media

Immunologic aspects of otitis media

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