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Correlation of Higher Antibody Levels to Pneumococcal Proteins with Protection from Pneumococcal Acute Otitis Media but Not Protection from Nasopharyngeal Colonization in Young Children

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Publisher Elsevier
Date 2017 Feb 2
PMID 28143785
Citations 6
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Abstract

Objectives: We previously found that nasopharyngeal (NP) colonization by Streptococcus pneumoniae elicits mucosal antibody responses to three protein vaccine candidates: pneumococcal histidine triad protein D (PhtD), pneumococcal choline-binding protein A (PcpA), and detoxified pneumolysin (PlyD1). Here we sought to determine if mucosal antibody levels to the proteins correlated with protection from acute otitis media (AOM) and NP colonization.

Methods: A total of 228 NP samples were prospectively collected from 100 healthy infants at 6-24 months of age. Whenever children were diagnosed with AOM, middle ear fluids were collected to confirm the diagnosis by microbiological culture. NP mucosal IgG and IgA were quantified by ELISA.

Results: Higher NP mucosal antibody levels to S. pneumoniae proteins correlated with significantly decreased likelihood of developing AOM caused by S. pneumoniae during 3 to 12 months of subsequent prospective monitoring. Specifically, children who did not experience AOM (n=111samples) caused by S. pneumoniae had two- to five-fold higher mucosal IgG levels to PcpA (all p values <0.01), six- to eight-fold higher IgA to PhtD (all p values <0.05); two- to three-folder higher IgA to PcpA (all p values <0.05), and two- to three-fold higher IgA to PlyD1 (p 0.08, p 0.03 and p 0.08) compared with children who did experience AOM (n=18samples). No association between mucosal antibody levels to the three proteins and NP colonization with S. pneumoniae was found.

Conclusion: Higher NP mucosal IgG levels to PcpA, and IgA to PhtD, PcpA and PlyD1 correlate with reduced risk of development of S. pneumoniae AOM infection but not with reduced risk of NP colonization in young children.

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References
1.
Bogaert D, de Groot R, Hermans P . Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004; 4(3):144-54. DOI: 10.1016/S1473-3099(04)00938-7. View

2.
Zhang Z, Clarke T, Weiser J . Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest. 2009; 119(7):1899-909. PMC: 2701860. DOI: 10.1172/JCI36731. View

3.
Simell B, Ahokas P, Lahdenkari M, Poolman J, Henckaerts I, Kilpi T . Pneumococcal carriage and acute otitis media induce serum antibodies to pneumococcal surface proteins CbpA and PhtD in children. Vaccine. 2009; 27(34):4615-21. DOI: 10.1016/j.vaccine.2009.05.071. View

4.
Lebon A, Verkaik N, Labout J, de Vogel C, Hooijkaas H, Verbrugh H . Natural antibodies against several pneumococcal virulence proteins in children during the pre-pneumococcal-vaccine era: the generation R study. Infect Immun. 2011; 79(4):1680-7. PMC: 3067559. DOI: 10.1128/IAI.01379-10. View

5.
Laufer A, Metlay J, Gent J, Fennie K, Kong Y, Pettigrew M . Microbial communities of the upper respiratory tract and otitis media in children. mBio. 2011; 2(1):e00245-10. PMC: 3031303. DOI: 10.1128/mBio.00245-10. View