Clin Vaccine Immunol. 2014 May 21. pii: CVI.00052-14. [Epub ahead of print]
Contributions to Protection from Streptococcus pneumoniae Infection Using Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD and PlyD1 in an Infant Murine Model During Challenge.
Verhoeven D1, Perry S1, Pichichero ME2.
Abstract
A vaccine consisting of several conserved proteins with different functions directing pathogenesis of pneumonia and sepsis would be preferred for protection against infection by Streptococcus pneumoniae. Infants will be the major population targeted for next generation pneumococcal vaccines. Here, we investigated the potential efficacy provided by from three recombinant pneumococcal vaccine candidate proteins; pneumococcal histidine triad D (PhtD), detoxified pneumolysin (PlyD1), and pneumococcal choline-binding protein A (PcpA), toward reducing pneumonia and sepsis in an infant mouse vaccine model. We found vaccination with PhtD and PcpA provided high IgG antibody titers after vaccination in infant mice, similar to adult mice comparators. PlyD1-specific total IgG was significantly lower in infant mice with minimal boosting with the second and third vaccinations. Similar isotypes of IgG for PhtD and PlyD1 were generated in infant compared to adult mice. Although lower total specific IgG was elicited to all three proteins in infant compared to adult mice, the infant mice were protected from bacteremic pneumonia and sepsis mortality (PlyD1) and had lower lung bacterial burdens (PcpA and PhtD) after challenge. The observed immune responses coupled with bacterial reductions elicited by each of the monovalent proteins support further testing in human infant clinical trials.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24850621
[PubMed - as supplied by publisher]
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