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Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life

BACKGROUND: Development of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority. Children living in low and lower-middle income settings...

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Autores principales: Martinovich, Kelly M., Rahman, Tasmina, de Gier, Camilla, Seppanen, Elke J., Orami, Tilda, Granland, Caitlyn M., Francis, Jacinta, Yoannes, Mition, Corscadden, Karli J., Ford, Rebecca, Jacoby, Peter, van den Biggelaar, Anita H. J., Bakaletz, Lauren O., Cripps, Allan W., Lehmann, Deborah, Richmond, Peter C., Pomat, William S., Kirkham, Lea-Ann S., Thornton, Ruth B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383109/
https://www.ncbi.nlm.nih.gov/pubmed/34447389
http://dx.doi.org/10.3389/fimmu.2021.725244
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author Martinovich, Kelly M.
Rahman, Tasmina
de Gier, Camilla
Seppanen, Elke J.
Orami, Tilda
Granland, Caitlyn M.
Francis, Jacinta
Yoannes, Mition
Corscadden, Karli J.
Ford, Rebecca
Jacoby, Peter
van den Biggelaar, Anita H. J.
Bakaletz, Lauren O.
Cripps, Allan W.
Lehmann, Deborah
Richmond, Peter C.
Pomat, William S.
Kirkham, Lea-Ann S.
Thornton, Ruth B.
author_facet Martinovich, Kelly M.
Rahman, Tasmina
de Gier, Camilla
Seppanen, Elke J.
Orami, Tilda
Granland, Caitlyn M.
Francis, Jacinta
Yoannes, Mition
Corscadden, Karli J.
Ford, Rebecca
Jacoby, Peter
van den Biggelaar, Anita H. J.
Bakaletz, Lauren O.
Cripps, Allan W.
Lehmann, Deborah
Richmond, Peter C.
Pomat, William S.
Kirkham, Lea-Ann S.
Thornton, Ruth B.
author_sort Martinovich, Kelly M.
collection PubMed
description BACKGROUND: Development of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority. Children living in low and lower-middle income settings are at the highest risk of contracting and dying from these diseases. Improved vaccines with broader coverage are required. Data on the natural development of antibodies to putative vaccine antigens, especially in high-risk settings, can inform the rational selection of the best antigens for vaccine development. METHODS: Serum IgG titres to four pneumococcal proteins (PspA1, PspA2, CbpA, and Ply) and five NTHi antigens (P4, P6, OMP26, rsPilA and ChimV4) were measured in sera collected from 101 Papua New Guinean children at 1, 4, 9, 10, 23 and 24 months of age using multiplexed bead-based immunoassays. Carriage density of S. pneumoniae and H. influenzae were assessed by quantitative PCR on genomic DNA extracted from nasopharyngeal swabs using species-specific primers and probes. All data were log-transformed for analysis using Student’s unpaired t-tests with geometric mean titre (GMT) or density (GMD) calculated with 95% confidence intervals (CI). RESULTS: Serum -pneumococcal protein-specific IgG titres followed a “U” shaped pattern, with a decrease in presumably maternally-derived IgG titres between 1 and 4 months of age and returning to similar levels as those measured at 1 month of age by 24 months of age. In contrast, NTHi protein-specific IgG titres steadily increased with age. There was no correlation between antibody titres and carriage density for either pathogen. CONCLUSION: This longitudinal study indicates that the waning of maternally- derived antibodies that is usually observed in infants, after infants does not occur for NTHi antigens in Papua New Guinean infants. Whether NTHi antigen IgG can be transferred maternally remains to be determined. Vaccines that are designed to specifically increase the presence of protective NTHi antibodies in the first few months of life may be most effective in reducing NTHi disease. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT01619462.
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spelling pubmed-83831092021-08-25 Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life Martinovich, Kelly M. Rahman, Tasmina de Gier, Camilla Seppanen, Elke J. Orami, Tilda Granland, Caitlyn M. Francis, Jacinta Yoannes, Mition Corscadden, Karli J. Ford, Rebecca Jacoby, Peter van den Biggelaar, Anita H. J. Bakaletz, Lauren O. Cripps, Allan W. Lehmann, Deborah Richmond, Peter C. Pomat, William S. Kirkham, Lea-Ann S. Thornton, Ruth B. Front Immunol Immunology BACKGROUND: Development of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority. Children living in low and lower-middle income settings are at the highest risk of contracting and dying from these diseases. Improved vaccines with broader coverage are required. Data on the natural development of antibodies to putative vaccine antigens, especially in high-risk settings, can inform the rational selection of the best antigens for vaccine development. METHODS: Serum IgG titres to four pneumococcal proteins (PspA1, PspA2, CbpA, and Ply) and five NTHi antigens (P4, P6, OMP26, rsPilA and ChimV4) were measured in sera collected from 101 Papua New Guinean children at 1, 4, 9, 10, 23 and 24 months of age using multiplexed bead-based immunoassays. Carriage density of S. pneumoniae and H. influenzae were assessed by quantitative PCR on genomic DNA extracted from nasopharyngeal swabs using species-specific primers and probes. All data were log-transformed for analysis using Student’s unpaired t-tests with geometric mean titre (GMT) or density (GMD) calculated with 95% confidence intervals (CI). RESULTS: Serum -pneumococcal protein-specific IgG titres followed a “U” shaped pattern, with a decrease in presumably maternally-derived IgG titres between 1 and 4 months of age and returning to similar levels as those measured at 1 month of age by 24 months of age. In contrast, NTHi protein-specific IgG titres steadily increased with age. There was no correlation between antibody titres and carriage density for either pathogen. CONCLUSION: This longitudinal study indicates that the waning of maternally- derived antibodies that is usually observed in infants, after infants does not occur for NTHi antigens in Papua New Guinean infants. Whether NTHi antigen IgG can be transferred maternally remains to be determined. Vaccines that are designed to specifically increase the presence of protective NTHi antibodies in the first few months of life may be most effective in reducing NTHi disease. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT01619462. Frontiers Media S.A. 2021-08-10 /pmc/articles/PMC8383109/ /pubmed/34447389 http://dx.doi.org/10.3389/fimmu.2021.725244 Text en Copyright © 2021 Martinovich, Rahman, de Gier, Seppanen, Orami, Granland, Francis, Yoannes, Corscadden, Ford, Jacoby, van den Biggelaar, Bakaletz, Cripps, Lehmann, Richmond, Pomat, Kirkham and Thornton https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Martinovich, Kelly M.
Rahman, Tasmina
de Gier, Camilla
Seppanen, Elke J.
Orami, Tilda
Granland, Caitlyn M.
Francis, Jacinta
Yoannes, Mition
Corscadden, Karli J.
Ford, Rebecca
Jacoby, Peter
van den Biggelaar, Anita H. J.
Bakaletz, Lauren O.
Cripps, Allan W.
Lehmann, Deborah
Richmond, Peter C.
Pomat, William S.
Kirkham, Lea-Ann S.
Thornton, Ruth B.
Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title_full Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title_fullStr Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title_full_unstemmed Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title_short Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
title_sort differences in pneumococcal and haemophilus influenzae natural antibody development in papua new guinean children in the first year of life
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383109/
https://www.ncbi.nlm.nih.gov/pubmed/34447389
http://dx.doi.org/10.3389/fimmu.2021.725244
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