23 research outputs found
Temporal development of the humoral immune response to surface antigens of Moraxella catarrhalis in young infants
The primary Moraxella catarrha/is-specific humoral immune response, and its association with nasopharyngeal colonization, was studied in a cohort of infants from birth to 2 years of age. Results indicated that the levels of antigen-specific IgG, IgA and IgM showed extensive inter-individual variability over time, with IgM and IgA levels to all 9 recombinant domains, from 7 different OMPs, being relatively low throughout the study period. In contrast, the level of antigen-specific IgG was significantly higher for the recombinant domains Hag(385-863), MID764-913, MID962-1200, UspA1(557-704) and UspA2(165-318) in cord blood compared to 6 months of age (P <= 0.001). This was a most likely a consequence of maternal transmission of antigen-specific IgG to newborn babies, possibly indicating a future role for these 3 surface antigens in the development of an effective humoral immune response to M. catarrhalis. Finally, at 2 years of age, the levels of antigen-specific IgG still remained far below that obtained from cord blood samples, indicating that the immune response to M. catarrhalis has not matured at 2 years of age. We provide evidence that a humoral antibody response to OMPs UspA1,UspA2 and Hag/MID may play a role in the immune response to community acquired M. catarrhalis colonization events. (C) 2011 Elsevier Ltd. All rights reserved
Omadacycline as a promising new agent for the treatment of infections with Mycobacterium abscessus
A model-informed preclinical approach for prediction of clinical pharmacodynamic interactions of anti-TB drug combinations
Fructose-bisphosphate aldolase and pyruvate kinase, two novel immunogens in Madurella mycetomatis
Eumycetoma, a chronic granulomatous disease characterized by a subcutaneous mass, multiple sinuses and purulent discharge containing grains, remains difficult to diagnose and treat. Madurella mycetomatis is the most common causative agent of eumycetoma. Using a serum pool from patients with active mycetoma, we screened a M. mycetomatis-specific lambda gt11 cDNA library which was shown to contain 8% of cDNA inserts encoding proteins involved in glycolysis. Two of these enzymes, fructose-bisphosphate aldolase (FBA) and pyruvate kinase (PK), were produced in vitro and their antigenicity was studied with bead-based flow cytometry. It appeared that both FBA and PK IgG antibodies were present in eumycetoma patient sera. However, only FBA antibody levels were found to be significantly higher in eumycetoma patient sera when compared to healthy Sudanese controls. Furthermore, FBA and PK were also found to be expressed on the hyphae present in the mycetoma grain. In conclusion, this study presents two new antigenic proteins of M. mycetomatis next to the translationally controlled tumour protein (TCTP): the glycolytic enzymes FBA and PK. These antigens might be useful as vaccine-candidates in the prevention of mycetoma
Contributions of capsule, lipoproteins and duration of colonisation towards the protective immunity of prior Streptococcus pneumoniae nasopharyngeal colonisation
Live attenuated vaccines have been proposed as a strategy to induce protective immunity against infectious diseases. Recent data have demonstrated that nasopharyngeal colonisation with Streptococcus pneumoniae induces protective immunity against subsequent invasive infection, suggesting nasal vaccination with live attenuated bacteria could be a preventative strategy. However the bacterial factors affecting the strength of this adaptive immune response remain unclear. In a direct comparison with the parent wild-type strain, we found that colonisation with bacteria lacking either capsule or surface lipoproteins led to significantly diminished protection. Immunity after colonisation was not dependent on serum IgG to capsular antigens. Colonisation density and duration was reduced for all the non-protective strains, suggesting that protective immunity maybe related to the extent of nasopharyngeal bacterial exposure. To investigate this hypothesis, we utilised an auxotrophic bacterial Delta pab strain where duration of colonisation could be controlled by supply and removal of para-amino-benzoic acid (PABA) to mouse drinking water. Supporting colonisation with the Delta pab strain for 5 days with PABA led to a faster serum antibody response compared to colonisation for less than 48 h. This enhanced immunogenicity was associated with a trend towards protection. The data presented here aid our understanding of why only certain live attenuated strains are able to function as effective vaccines, and may be valuable in informing the constituents of future live attenuated vaccines. (C) 2012 Elsevier Ltd. All rights reserved
Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses
Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis