Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans.

Vaccine
M Nadeem Khan, Michael E Pichichero

Abstract

We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE- isogenic mutants, a 40% (p=0.001) and 42% (p=0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of Escherichia coli and demonstrated that when PhtD and PhtE were surface expressed on E. coli, adherence increased to D562 and A549 cells, compared with the E. coli parent strain (p=0.005, 0.013 for D562 and p=0.034, p=0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1μg of IgG Fab from adult sera led to a 34% reduction (p=0.002) and from children a 20% (p=0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera...Continue Reading

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Citations

Jul 31, 2013·Critical Reviews in Microbiology·Michelle DarrieuxLuciana Cezar de Cerqueira Leite
Nov 6, 2015·Human Vaccines & Immunotherapeutics·Michael E PichicheroQingfu Xu
Jul 24, 2012·Trends in Microbiology·Charles D PlumptreJames C Paton
Nov 5, 2015·Human Vaccines & Immunotherapeutics·Kristin Moffitt, Richard Malley
Feb 11, 2015·Human Vaccines & Immunotherapeutics·M Nadeem Khan, Michael E Pichichero
Feb 19, 2015·Human Vaccines & Immunotherapeutics·Dabin RenMichael E Pichichero
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Dec 7, 2016·Molecular Medicine Reports·Sara NovickYaffa Mizrachi Nebenzahl
Aug 15, 2018·Nucleic Acids Research·Jelle SlagerJan-Willem Veening
Oct 14, 2017·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·D C AndradeC M Nascimento-Carvalho
Jan 13, 2019·Journal of Biomolecular Structure & Dynamics·Hesam DorostiYounes Ghasemi
Jun 25, 2015·Microbiology Spectrum·Donald N Forthal
Jul 19, 2021·Microbial Pathogenesis·Lazara Elena Santiesteban-LoresEneas Carvalho

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