Dataset Information

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.

ABSTRACT: Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen Streptococcus pneumoniae target the bacterial capsular polysaccharide and confer no protection against nonencapsulated strains or capsular types outside vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here, we report that a protein-based vaccine, a fusion construct of epitopes of CbpA to pneumolysin toxoid, confers effective protection against pneumococcal acute otitis media for non-PCV-13 serotypes and enhances protection for PCV-13 serotypes when coadministered with PCV-13. Having cross-reactive epitopes, the fusion protein also induces potent antibody responses against nontypeable Haemophilus influenzae and S. pneumoniae, engendering protection against acute otitis media caused by emerging unencapsulated otopathogens. These data suggest that augmenting capsule-based vaccination with conserved, cross-reactive protein-based vaccines broadens and enhances protection against acute otitis media.

SUBMITTER: Rowe HM

PROVIDER: S-EPMC6759292 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.

Rowe Hannah M HM Mann Beth B Iverson Amy A Poole Aaron A Tuomanen Elaine E Rosch Jason W JW

Infection and immunity 20190919 10

Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen <i>Streptococcus pneumoniae</i> target the bacterial capsular polysaccharide and confer no protection against nonencapsulated strains or capsular types outside vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here, we report that a protein-based vaccine, a fusion construct of epitop ...[more]

PMID: 31308088

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Project description:Nontypeable Haemophilus influenzae (NTHi) colonize the human pharynx asymptomatically, and are also an important cause of otitis media (OM). Previous studies have demonstrated that some genes are more prevalent in OM-causing NTHi strains than in commensal strains, suggesting a role in virulence. These studies, however, are unable to investigate the possible associations between gene polymorphisms and disease. This study examined amino acid polymorphisms and sequence diversity in a potential virulence gene, the hemin receptor hemR, from a previously characterized NTHi strain collection containing both commensal and OM organisms to identify possible associations between the polymorphisms and otitis media. The full open reading frame of hemR was sequenced from a total of 146 NTHi isolates, yielding a total of 47 unique HemR amino acid sequences. The predicted structure of HemR showed substantial similarity to a class of monomeric TonB dependent, ligand-gated channels involved in iron acquisition in other gram negative bacteria. Fifteen amino acid polymorphisms were significantly more prevalent at the 90% confidence level among commensal compared to OM isolates. Upon controlling for the confounding effect of population structure, over half of the polymorphism-otitis media relationships lost statistical significance, emphasizing the importance of assessing the effect of population structure in association studies. The seven polymorphisms that retained significance were dispersed throughout the protein in various functional and structural domains, including the signal peptide, N-terminal plug domain, and intra- and extracellular loops. The alternate amino acid of only one of these seven polymorphisms was more common among OM isolates, demonstrating a strong trend toward the consensus sequence among disease causing NTHi. We hypothesize that variability at these positions in HemR may result in a reduced ability to acquire iron, rendering NTHi with such versions of the gene less fit for survival in the middle ear environment.

Dataset Information

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.

Publications

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.

Similar Datasets

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