Generating a pneumococcal vaccine that is serotype independent and cost effective remains a global challenge. γ-Irradiation has been used widely to sterilize biological products. It can also be utilized as an inactivation technique to generate whole-cell bacterial and viral vaccines with minimal impact on pathogen structure and antigenic determinants. In the present study, we utilized γ-irradiation to inactivate an un-encapsulated Streptococcus pneumoniae strain Rx1 with an unmarked deletion of the autolysin gene lytA and with the pneumolysin gene ply replaced with an allele encoding a non-toxic pneumolysoid (PdT) (designated γ-PN vaccine). Intranasal vaccination of C57BL/6 mice with γ-PN was shown to elicit serotype-independent protection in lethal challenge models of pneumococcal pneumonia and sepsis. Vaccine efficacy was shown to be reliant on B-cells and interleukin (IL)-17A responses. Interestingly, immunization promoted IL-17 production by innate cells not T helper 17 (Th17) cells. These data are the first to report the development of a non-adjuvanted intranasal γ-irradiated pneumococcal vaccine that generates effective serotype-independent protection, which is mediated by both humoral and innate IL-17 responses.
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May 2016
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Paraffin section of knee joint from CIA mouse model. Safranin-O/fast green staining showed significant cartilage degeneration and bone erosion in femorotibial joint. For further details see pp. 667-681. Image kindly provided by Dr. Chih-Hsin Tang.
Research Article|
March 18 2016
Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses
Rachelle Babb;
Rachelle Babb
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Austen Chen;
Austen Chen
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Timothy R. Hirst;
Timothy R. Hirst
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
†Gamma Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT 2600, Australia
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Ervin E. Kara;
Ervin E. Kara
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Shaun R. McColl;
Shaun R. McColl
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Abiodun D. Ogunniyi;
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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James C. Paton;
James C. Paton
2
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
Correspondence: Mohammed Alsharifi (email [email protected]) or James C. Paton ([email protected]).
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Mohammed Alsharifi
Mohammed Alsharifi
2
*Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
†Gamma Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT 2600, Australia
Correspondence: Mohammed Alsharifi (email [email protected]) or James C. Paton ([email protected]).
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Publisher: Portland Press Ltd
Received:
October 01 2015
Revision Received:
January 25 2016
Accepted:
February 01 2016
Accepted Manuscript online:
February 01 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (9): 697–710.
Article history
Received:
October 01 2015
Revision Received:
January 25 2016
Accepted:
February 01 2016
Accepted Manuscript online:
February 01 2016
Citation
Rachelle Babb, Austen Chen, Timothy R. Hirst, Ervin E. Kara, Shaun R. McColl, Abiodun D. Ogunniyi, James C. Paton, Mohammed Alsharifi; Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses. Clin Sci (Lond) 1 May 2016; 130 (9): 697–710. doi: https://doi.org/10.1042/CS20150699
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