Vaccine. 2016 Nov 2. pii: S0264-410X(16)30996-3. doi: 10.1016/j.vaccine.2016.10.061. [Epub ahead of print]

In vivo screen of genetically conserved Streptococcus pneumoniae proteins for protective immunogenicity.

Anderson RJ1, Guru S1, Weeratna R2, Makinen S2, Falconer DJ1, Sheppard NC1, Lang S1, Chang B1, Goenaga AL1, Green BA3, Merson JR1, Gracheck SJ1, Eyles JE4.

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Abstract

We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA.

Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS:

Antibody; Antigen; Immunity; Pneumococcal; Pneumococcus; Vaccine

PMID: 27816374 DOI: 10.1016/j.vaccine.2016.10.061

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