title: Enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine.
abstract: Streptococcus pneumoniae and influenza are the world's foremost bacterial and viral respiratory pathogens. We have previously described a γ-irradiated influenza A virus (γ-FLU) vaccine that provides cross-protective immunity against heterosubtypic infections. More recently, we reported a novel non-adjuvanted γ-irradiated S pneumoniae (γ-PN) vaccine that elicits serotype-independent protection. Considering the clinical synergism of both pathogens, combination of a serotype-independent pneumococcal vaccine with a broad-spectrum influenza vaccine to protect against both infections would have a considerable clinical impact. In the present study, we co-immunized C57BL/6 mice intranasally (IN) with a mixture of γ-PN (whole inactivated cells) and γ-FLU (whole inactivated virions) and examined protective efficacy. Co-immunization enhanced γ-PN vaccine efficacy against virulent pneumococcal challenge, which was dependent on CD4+T-cell responses. In contrast, vaccination with γ-PN alone, co-immunization enhanced pneumococcal-specific effector T-helper 17 cell (Th17) and Th1 memory cell, promoted development of CD4+tissue-resident memory (TRM) cells and enhanced Pneumococcus-specific antibody responses. Furthermore, co-immunization elicited significant protection against lethal influenza challenge, as well as against co-infection with both influenza and S pneumoniae. This is the first report showing the synergistic effect of combining whole cell and whole virion vaccines to both S pneumoniae and influenza as a single vaccine to protect against individual and co-infection, without compromising pathogen-specific immunity.
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Babb
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Austen
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, 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: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Ervin E
authors.initials: EE
authors.lastname: Kara
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia mohammed.alsharifi@adelaide.edu.au) james.paton@adelaide.edu.au).|Gamma Vaccines Pty Ltd., Mountbatten Park, Yarralumla ACT 2600, Australia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alsharifi
authors.affiliation: Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, 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
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology; D014611:Vaccination
chemical_list: D007252:Influenza Vaccines; D022242:Pneumococcal Vaccines
keywords: Streptococcus pneumoniae; co-infection; combination vaccine; influenza A virus; protective immunity