The Immune Response to Acute Otitis Media in Children. II. Serum and Middle Ear Fluid Antibody in Otitis Media Due to Haemophilus influenzae

Sloyer, John L.; Cate, Charles C.; Howie, Virgil M.; Ploussard, John H.; Johnston, Richard B.

doi:10.1093/infdis/132.6.685

Cited by 60 publications

(26 citation statements)

References 10 publications

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“…The incidence of culture-positive effusions from the contralateral unchallenged ears (bilateral effusion) was 5% in the group challenged with wt BCH-3 and 62% in the group challenged with the isogenic BCH-3 ompP1 mutant on days 6 and 8 (P ϭ 0.0045). (71,72). These results are paralleled by our study of an adult patient indicating that the majority of serum bactericidal antibody activity after recovery from NTHI disease was directed to OMPs (24).…”

Section: Discussionsupporting

confidence: 71%

“…Disease in infants typically begins after maternal antibodies have dissipated and before their own immune systems are fully matured (42) (15) are efficacious, unencapsulated NTHI remains responsible for ϳ30% of the Ͼ45 million episodes of acute bacterial otitis media yearly in North America and Europe (43,45,58,68) and is implicated in as many as ϳ20% of the 4 million fatal acute respiratory infections per annum worldwide occurring mostly in children (9). Studies of these infections demonstrate that NTHI usually elicits bactericidal antibodies (71,72). However, protection appears to be strain specific, with a P values are based on a comparison of data for chinchillas immunized with rP1 plus adjuvant with those for chinchillas immunized with adjuvant alone, as determined by the Fisher exact test (80).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to NontypeableHaemophilus influenzae: an Unambiguous, Multifaceted Approach

et al. 2000

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Candidate vaccine antigens for preventing otitis media caused by nontypeable Haemophilus influenzae (NTHI) should possess one or more conserved epitopes. We sought to evaluate the candidacy of P1, a surface-expressed outer membrane protein knowing that this antigen is subject to diversifying selection. Therefore, we selected NTHI strains from among >500 phylogenically variant isolates representative of the diversity found in natural populations of H. influenzae. Twenty-three variants of P1 (<95% similarity) were identified among 42 strains. When chinchillas were immunized with recombinant P1 (rP1) obtained from one of these isolates (BCH-3), all animals developed antibodies specific for rP1. Immunized animals were protected against disease when challenged with BCH-3, but not with an ompP1 mutant of BCH-3 or a strain (BCH-2) possessing a heterologous P1 (91% identity). We conclude that (i) while P1 induces protection against NTHI-mediated otitis media, development of a polyvalent vaccine reflecting the variability of P1 would be necessary to construct an efficacious vaccine and (ii) use of a phylogenically characterized collection of representative isolates in concert with gene sequencing, cloning, gene inactivation, and animal testing offers an efficient, rational, and rigorous strategy for evaluating the potential problems associated with variability of vaccine targets and specificity of related immune responses.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to NontypeableHaemophilus influenzae: an Unambiguous, Multifaceted Approach

et al. 2000

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“…Investigators published two elegant studies in the 1970s that strongly suggested local production of pathogen-specific antibodies was occurring in the middle ear space of children with AOM (7,28). Our results are not inconsistent with their observations since they did not investigate the possibility that the origin of the pathogen-specific antibodies identified in the middle ear space of children with AOM were not from local production but rather from reflux of nasopharyngeal secretions.…”

Section: Discussioncontrasting

confidence: 54%

Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Kaur¹,

Kim²,

Casey³

et al. 2012

Clin. Vaccine Immunol.

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The human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. C olonization of the nasopharynx (NP) by respiratory bacterial pathogens produces both a systemic and a mucosal immune response (1,10,11,15,22,26,38). Local mucosal immunity in the NP plays a crucial role in the reduction of carriage and prevention of local disease (acute otitis media [AOM], sinusitis, and pneumonia) and systemic invasion by respiratory bacteria (4, 16, 20-22, 27, 36). Protective mucosal immune responses are most effectively induced by mucosal immunization through oral and nasal routes but the vast majority of vaccines in use today are administered by injection (19). Parenteral administration of Haemophilus influenzae type b and Streptococcus pneumoniae polysaccharide and polysaccharide-conjugate vaccines can induce a transient mucosal immune response but immunologic memory at the mucosal level is generally not induced (23,24,37).Current pneumococcal conjugate vaccines for prevention of AOM and pneumonia are administered by injection and are considered to be effective by generation of antibody in serum and transudation of antibody to the NP, middle ear, and lung (3,12,25,34,37). New vaccines for the prevention of Streptococcus pneumoniae and nontypeable Haemophilus influenzae AOM and other mucosal infections are in development (2, 6, 11, 21, 22). Therefore, the sources of antibody at the site of infection (the middle ear) need to be understood.Although the normal mucosa of the middle ear possesses neither immunocompetent lymphocytes nor associated lymphoid tissues, there are studies which have demonstrated the presence of secretory IgA (sIgA) in middle ear effusions and IgA plasma cells in the mucosa of the middle ear suggesting that a local immune response in the middle ear is possible and may contribute to resolution of or protection from infection (8,9,18). Previous studies have also shown severalfold more IgG antibody compared to IgA antibody in the middle ear, suggesting that antibodies in the middle ear arrive by transudation from serum (33). In the present study, we evaluated (i) simultaneous concentrations of IgG and IgA in serum, NW, and MEF samples in children with AOM; (ii) simultaneous concentrations of sIgA in NW and MEF samples; and (iii) the electrophoresis pattern of the entire array of IgA antibodies in the MEF and NW to determine whether the antibodies present in middle ear fluid were predominantly derived from serum and the nasal passageways by reflux up the Eustachian tube. MATERIALS AND METHODSPatient popul...

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“…Although the sensitivity of the antibody assay varied among the different immunoglobulin classes, the differences were insufficient to account for the degree of dominance of the IgG type of antibody. Specific immunoglobulins of the G, M, and A classes have been identified previously in MEF of children with pneumococcal and H. influenzae OME; organism-specific IgG antibody was similarly the more common immunoglobulin class detected in both types of infection (22,23).…”

Section: Resultssupporting

confidence: 54%

Otitis media in children: Local immune response to nontypeable Haemophilus influenzae

1990

International Journal of Pediatric Otorhinolaryngology

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Twenty children experienced 30 episodes of otitis media with effusion due to nontypeable (NT) Haemophilus influenzae in the first 2 years of life. The local and systemic immune responses to homologous strains of NT H. influenzae were determined by an immunodot assay. Strain-specific immunoglobulin G (IgG) antibody predominated in the middle ear fluid (MEF). It was detected in 91% of the children, compared with IgM in 48% (P < 0.005), IgA in 52% (P < 0.005), and secretory IgA in 18% (P < 0.005). The titer (log2) of NT H. influenzae-specific IgG antibody (mean standard error, 8.2 + 0.1) exceeded the titers of IgM (3.4 0.1), IgA (3.7 0.1), and secretory IgA (1.2 + 0.3). NT H. influenzae-specific antibody was detected exclusively in MEFs of individuals who possessed homologous serum antibody. Although antibody titers in MEF declined over time, serum antibody titers remained stable. These data suggest that immunity to NT H. influenzae in the middle ear, in part, reflects systemic immunity. Whereas local antibody disappears after resolution of the infection, systemic antibody persists.Otitis media with effusion (OME) is among the most common illnesses that affect young children. Approximately 60 to 70% of children experience OME during the first 3 years of life, and at least 40% of them experience more than one episode (26). The incidence of OME is highest in the first 2 years of life and then declines (10). Presumably, immunity plays a role in the reduction of the frequency of OME.Three bacterial species-Streptococcus pneumoniae, nontypeable (NT) Haemophilus influenzae, and Branhamella catarrhalis-account for the majority of identifiable bacterial causes of acute OME (2,3,(18)(19)(20). NT Haemophilus influenzae is responsible for a major share of recurrent episodes of OME (9,11). Recent studies have suggested that NT H. influenzae consists of many different strains that may be characterized by their outer membrane proteins (13-16). Immunity to NT H. influenzae appears to be strain specific and directed to the outer membrane proteins (1,5,6,8,15,17). Susceptibility and resistance to the development of NT H. influenzae OME have been associated with the presence and absence of serum bactericidal antibody (1,8,21). Less is known about the role of local immunity in NT H. influenzae OME.The present study was designed to examine the local development of immunoglobulin G (IgG), IgM, IgA, and secretory IgA (sIgA) antibodies to homologous strains of NT H. influenzae in the middle ear during active infection. The study also analyzed humoral response to NT H. influenzae over a prolonged period of convalescence. MATERIALS AND METHODSGeneral design. A total of 220 children were enrolled in a prospective study of otitis media. At enrollment, 39% were s6 months old, 32% were 7 to 12 months old, and 29% were >12 months old. At the time of entry into the study, 32% had experienced no OME, 51% had had one to five episodes of OME, and 17% had had more than five episodes of OME. During 3 years of monitoring the children, 320 tympanocen-*...

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The Immune Response to Acute Otitis Media in Children. II. Serum and Middle Ear Fluid Antibody in Otitis Media Due to Haemophilus influenzae

Cited by 60 publications

References 10 publications

Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to NontypeableHaemophilus influenzae: an Unambiguous, Multifaceted Approach

Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to NontypeableHaemophilus influenzae: an Unambiguous, Multifaceted Approach

Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Otitis media in children: Local immune response to nontypeable Haemophilus influenzae

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