Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria

Zhang, Qibo; Finn, Adam

doi:10.1136/jcp.2004.016253

Cited by 34 publications

(17 citation statements)

References 101 publications

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“…The nasopharyngeal carriage of pneumococci is also a prerequisite of infection and invasive diseases and is the source of transmission (53). Therefore, local mucosal immunity within the nasopharynx may play a crucial role in the reduction of carriage.…”

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confidence: 99%

Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae

Dai

Wang

et al. 2011

Clin Vaccine Immunol

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Streptococcus pneumoniae is a respiratory pathogen, and mucosal immune response plays a significant role in the defense against pneumococcal infections. Thus, intranasal vaccination may be an alternative approach to current immunization strategies, and effective delivery systems to mucosal organism are necessary. In this study, BALB/c mice were immunized intranasally with chitosan-DNA nanoparticles expressing pneumococcal surface antigen A (PsaA). Compared to levels in mice immunized with naked DNA or chitosan-pVAX1, anti-PsaA IgG antibody in serum and anti-IgA antibody in mucosal lavages were elevated significantly in mice immunized with chitosan-psaA. The balanced IgG1/IgG2a antibody ratio in serum, enhanced gamma interferon (IFN-␥) and IL-17A levels in spleen lymphocytes, and mucosal washes of mice immunized with chitosan-psaA suggested that cellular immune responses were induced. Furthermore, significantly fewer pneumococci were recovered from the nasopharynx of mice immunized with chitosan-psaA than for the control group following intranasal challenge with ATCC 6303 (serotype 3). These results demonstrated that mucosal immunization with chitosan-psaA may successfully generate mucosal and systemic immune responses and prevent pneumococcal nasopharyngeal colonization. Hence, a chitosan-DNA nanoparticle vaccine expressing pneumococcal major immunodominant antigens after intranasal administration could be developed to prevent pneumococcal infections.

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confidence: 99%

Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae

Dai

Wang

et al. 2011

Clin Vaccine Immunol

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“…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).…”

mentioning

confidence: 99%

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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“…[4][5][6] A more likely explanation is the fact that we considered antibody concentrations from children up to 93 months old, who received their last dose of Hib vaccine at six months of age.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence suggests that while anti-capsular IgG concentrations >0.15 mg/mL may protect against invasive Hib disease, concentrations >5 mg/mL may be necessary to protect against Hib oropharyngeal carriage. [3][4][5][6][7] A concentration of 1 mg/mL is considered by some authors as the long-term protective threshold against Hib disease. 3,7,8 In unvaccinated children serum antibodies to PS are developed starting at two years of age in response to subclinical infections and to carriage.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 Low carriage in turn provides stimuli favoring herd immunity mechanisms to play a major role. 4,6 To induce long-lasting herd immunity, the effect of vaccination on carriage should carry over to school-aged children. If the aforementioned is not achieved and a booster dose is not given, residual cases of Hib disease may emerge among unvaccinated individuals.…”

Section: Introductionmentioning

confidence: 99%

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Anticapsular Polysaccharide IgG Concentrations in Mexican Children Formerly Immunized with Haemophilus Influenzae b Prp-T Vaccine

León¹,

García²,

Arredondo³

et al. 2007

Human Vaccines

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Background: In 1999 H. influenzae b (Hib) PRP-T vaccine was introduced into primary immunization schedule in Mexico. There have been no studies evaluating antibody response after widespread immunization in our country. It is now recognized that Hib conjugates induce significant initial antibody levels that in some cases wane over time. This study relies on the measurement of IgG serum antibody concentrations to Hib capsular polysaccharide (PS) and is interpreted in the light of the accepted levels ≥0.15 mg/mL for short-term protection against Hib invasive disease and ≥5.0 mg/mL for protection against Hib oropharyngeal carriage.Methods: Using a validated ELISA assay, we measured the IgG serum antibody concentrations in 115 children between 7 and 93 months of age who had received three doses of PRP-T. We used the standard reference serum US FDA 1983 for quantification of PS antibody levels. Concentrations were estimated using 3 rd degree polynomial regression lines. As there was no unvaccinated group available (>95% of Mexican children have received the Hib vaccine), the study was designed as a cross-sectional.Results: All children had serum IgG concentrations ≥0.15 mg/mL [range 0.24-54.64 mg/mL]; 69.6 % (80/115) had ≥1.0 mg/mL and 14% (16/115) showed concentrations ≥5.0 mg/mL. The vaccine elicited geometric mean concentrations (GMC) of 4.0, 1.6, 1.4 and 2.4 mg/mL in groups of 7-12, 13-24, 25-48 and 49-93 month-old respectively.Conclusions: PRP-T vaccination in this group of Mexican children has resulted in serum IgG concentrations ≥0.15 mg/mL, suggesting that Hib immunization has conferred protection against invasive disease.

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Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria

Cited by 34 publications

References 101 publications

Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae

Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae

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

Anticapsular Polysaccharide IgG Concentrations in Mexican Children Formerly Immunized with Haemophilus Influenzae b Prp-T Vaccine

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