title: Reducing the impact of influenza-associated secondary pneumococcal infections.
abstract: When administered prophylactically, we show that the Toll-like receptor-2 (TLR-2) agonist PEG-Pam2Cys (pegylated-S-(2,3-bis(palmitoyloxy)propyl)cysteine) not only mediates potent anti-viral activity against influenza virus but also reduces the impact of secondary infections with Streptococcus pneumoniae (the pneumococcus) by reducing (i) pulmonary viral and bacterial burdens, (ii) the levels of proinflammatory cytokines that normally accompany influenza and S. pneumoniae secondary infections and (iii) the vascular permeability of the pulmonary tract that can allow bacterial invasion of the blood in mice. We also show that an inactivated detergent-disrupted influenza virus vaccine formulated with the Pam2Cys-based adjuvant R4-Pam2Cys provides the host with both immediate and long-term protection against secondary pneumococcal infections following influenza virus infection through innate and specific immune mechanisms, respectively. Vaccinated animals generated influenza virus-specific immune responses that provided the host with long-term protection against influenza virus and its sequelae. This vaccine, which generates an immediate response, provides an additional countermeasure, which is ideal for use even in the midst of an influenza outbreak.
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Edin J
authors.initials: EJ
authors.lastname: Mifsud
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Amabel C
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Kirsty R
authors.initials: KR
authors.lastname: Short
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Brendon Y
authors.initials: BY
authors.lastname: Chua
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Jackson
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D007109:Immunity / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000150:complications* / Q000276:immunology; D011008:Pneumococcal Infections / Q000097:blood / Q000150:complications* / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000276:immunology; D016019:Survival Analysis; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D018925:Chemokines; D000939:Epitopes; D018836:Inflammation Mediators; D055666:Lipopeptides; C552442:S-(2,3-bis(palmitoyloxy)propyl)cysteine; D011092:Polyethylene Glycols