ABSTRACT
Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses.
Subject(s)
Adaptive Immunity , Antibodies, Bacterial/biosynthesis , Bordetella Infections/immunology , Gene Expression Regulation/immunology , Immunity, Innate , Lung/immunology , Animals , Bordetella Infections/genetics , Bordetella Infections/microbiology , Bordetella Infections/pathology , Bordetella pertussis/immunology , Complement Activation , Cytokines/genetics , Cytokines/immunology , Female , Host-Pathogen Interactions/immunology , Immunoglobulin A/biosynthesis , Immunologic Memory , Lung/microbiology , Lung/pathology , Mice , Mice, Inbred BALB C , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Spleen/immunology , Spleen/microbiology , Spleen/pathology , Th1 Cells/immunology , Th1 Cells/microbiology , Th1 Cells/pathology , Th17 Cells/immunology , Th17 Cells/microbiology , Th17 Cells/pathology , Transcription Factors/genetics , Transcription Factors/immunology , alpha-Defensins/genetics , alpha-Defensins/immunologyABSTRACT
In the context of eradication of poliomyelitis the World Health Organization stimulates the development of inactivated polio vaccines based on attenuated virus strains. In addition to vaccine development, tests have to be designed to assess the vaccine quality. An important test is the identification test for poliovirus strains that are used for the vaccine production. A rapid and accurate PCR method with fluorescent probes has been developed to identify unequivocally the vaccine-specific poliovirus strains, such as Mahoney, MEF-1, Saukett H, Sabin type 1, Sabin type 2 and Sabin type 3.
