title: Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses.
abstract: 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.
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Babb
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Austen
authors.initials: A
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hirst
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Ervin E
authors.initials: EE
authors.lastname: Kara
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.affiliation: Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia mohammed.alsharifi@adelaide.edu.au james.paton@adelaide.edu.au.
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.affiliation: 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 mohammed.alsharifi@adelaide.edu.au james.paton@adelaide.edu.au.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alsharifi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005720:Gamma Rays; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018805:Sepsis / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology* / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D020381:Interleukin-17; D022242:Pneumococcal Vaccines; D007371:Interferon-gamma
keywords: Streptococcus pneumoniae; protective immunity; serotype independent; vaccine