title: Polyvalent 23 epitope polysaccharide pneumonia vaccine induced effective protection through strain-adapted effector mechanisms as demonstrated by the different cytokine responses in mice challenged with two different strains of Streptococcus pneumoniae.
abstract: We used a Balb/c mouse model of pneumococcal pneumonia to investigate the protection mechanisms induced by immunization with a polyvalent 23 epitope polysaccharide pneumonia vaccine. Groups of mice were injected x 4 times s.c. within one month, with this vaccine preparation. Mice were subsequently challenged at day 45, with a lethal, intratracheal inoculum of two strains of Streptococcus pneumoniae - either a highly virulent and strongly immunogenic serotype 3 strain (P4241), or a less virulent and weakly immunogenic serotype 19F strain (P15986). The intratracheal S. pneumoniae challenge-induced lethality, antibody response, bacterial clearance, and cytokine secretions were monitored to analyze the strain-adapted effector mechanisms. Pulmonary levels of TNFalpha, IL-6, IL-1 beta, MIP-1 alpha, KC, MCP-1/JE and MIP-2 cytokines were determined up to 48 hours post-infection. Survival rates were 82% and 100% among vaccinated animals challenged at day 45 with P4241, and P1598 mice respectively, and 0% in non-vaccinated mice (p<0.001). Survival was associated with a rapid bacterial clearance from blood and lungs, which similar for the two strains. Immunization induced a serotype-specific antibody response. Kinetics of the cytokine profile in the lung following intratracheal inoculation with the 4241 strain was different in animals vaccinated 45 days previously, compared to naïve, control mice. Generally speaking the bacterial-induced inflammatory cytokine response induced with the 4241 strain was much weaker in vaccinated animals than in control mice. The only cytokines showing a greater increase in vaccinated mice compare to control animals were IL-1 beta, KC and MCP-1. Production of TNFalpha and IL-6 was lower in vaccinated animals than in controls. At variance with the previous bacteria strain-induced cytokine profile, infection with the P15986 strain induced a strong inflammatory response, with a substantial increase in all the cytokine tested, which was similar in vaccinated and in naïve, control animals, except for MIP-1 alpha, which was the only mediator significantly more produced by vaccinated animals than by naïve, control mice following P15986 infection. The distinct cytokine profiles, which were observed in this study depending upon the two strains of S. pneumoniae used for challenge, demonstrated that protection against each strain was obtained through a different defence strategy.
authors.affiliation: EA3964, UFR Médicale, Université Paris VII-Denis Diderot, BP 416, 16 rue H. Huchard, 75870 Paris Cedex 18, France. jmohler@bichat.inserm.fr
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mohler
authors.forename: Pierre
authors.initials: P
authors.lastname: Moine
authors.forename: Esther
authors.initials: E
authors.lastname: Azoulay-Dupuis
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Bruno
authors.initials: B
authors.lastname: Fantin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007114:Immunization / Q000379:methods; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007700:Kinetics; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016207:Cytokines; D000939:Epitopes; D053583:Interleukin-1beta; D015850:Interleukin-6; D022242:Pneumococcal Vaccines; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha