title: Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection.
abstract: An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S. pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouse-adapted H1N1 influenza A virus (PR/8/34). S. pneumoniae established effective commensal colonization, and influenza virus coinfection caused S. pneumoniae NP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction of S. pneumoniae NP density (>2.5 log units) than PhtD vaccination (∼1-log-unit reduction). However, no significant difference was observed with regard to the prevention of S. pneumoniae bacteremia, and there was no difference in mortality. Depletion of CD4+T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4+T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4+T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasive S. pneumoniae pathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.
authors.affiliation: Center for Infectious Disease and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA nadeem.khan@rochesterregional.org.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Khan
authors.affiliation: Center for Infectious Disease and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Center for Infectious Disease and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002353:Carrier State; D060085:Coinfection; D004195:Disease Models, Animal; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009305:Nasopharynx / Q000276:immunology* / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines
keywords: pneumococcal