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Presence of IS1301 in the capsule biosynthesis locus in meningococcal carriage and disease isolates from UK
Journal of Infection (2010) 61, 516e525
www.elsevierhealth.com/journals/jinf
First session: Chairs & discussants Professor David Dockrell (Sheffield) & Professor Dietrich Mack (Swansea) previously found in MenC. IS1301 can be inserted in the opposite orientation and is always associated with novel polymorphisms. Human serum assays showed that IS1301 with novel polymorphisms in the IGR did not mediate enhanced resistance to human serum.
1 PRESENCE OF IS1301 IN THE CAPSULE BIOSYNTHESIS LOCUS IN MENINGOCOCCAL CARRIAGE AND DISEASE ISOLATES FROM UK Kugelberg Elisabeth 1, Gollan Bridget 1, Farrance Christopher 1, Bratcher Holly 2, Lucidarme Jay 3, Ibarz-Pavon Ana Belen 2, Maiden Martin 2, Borrow Ray 3, Tang Christoph
Conclusions 1
1
Imperial College London, UK 2 University of Oxford, UK 3 Health Protection Agency, Manchester, UK
Introduction The complement system is critical for immunity against the human pathogen Neisseria meningitidis. The current polysaccharide conjugate vaccine against serogroup C N. meningitidis (MenC) has lead to a striking decrease in disease caused by this serogroup. We have previously identified MenC strains, isolated in Spain from invasive cases, which avoid killing by bactericidal antibodies in vaccinees’ sera. These isolates were shown to have an insertion of IS1301 in the intergenic region (IGR) between the operons necessary for capsule biosynthesis and export. Insertion of IS1301 leads to increased amount of polysaccharide capsule and thereby increased protection against complement-mediated killing.
Methods and results PCR and sequencing was used to screen >1500 meningococcal carriage and disease isolates from UK for the presence of IS1301 in the IGR. IS1301 was not found in the IGR of MenC vaccine failures but was frequent among serogroup B N. meningitidis (MenB) isolates. Interestingly IS1301 found in UK MenB isolates all differed from IS1301 0163-4453/$36 doi:10.1016/j.jinf.2010.09.005
MenC disease in UK vaccine failures is not caused by isolates with IS1301 in the IGR. There is no significant difference for the presence of IS1301 in the IGR of MenB disease isolates compared to carriage isolates. IS1301 with associated novel polymorphisms in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.
2 THE VACCINE ANTIGEN FACTOR H BINDING PROTEIN FROM NEISSERIA MENINGITIDIS CAN BE MODIFIED TO REDUCE BINDING TO FACTOR H WITH NO CHANGE IN IMMUNOGENICITY Tan Lionel 1, Caesar Joe 2, Li Yanwen 1, Exley Rachel 1, Kugelberg Elisabeth 1, Zhang Qian 1, Yan Gabriel 1, Lea Susan 2, Tang Christoph 1 1
Centre for Molecular Microbiology & Infection, Imperial College London, UK 2 Sir William Dunn School of Pathology, University of Oxford, UK
Introduction Neisseria meningitidis recruits the negative complement regulator, factor H (fH),to its surface via factor H binding
www.elsevierhealth.com/journals/jinf
First session: Chairs & discussants Professor David Dockrell (Sheffield) & Professor Dietrich Mack (Swansea) previously found in MenC. IS1301 can be inserted in the opposite orientation and is always associated with novel polymorphisms. Human serum assays showed that IS1301 with novel polymorphisms in the IGR did not mediate enhanced resistance to human serum.
1 PRESENCE OF IS1301 IN THE CAPSULE BIOSYNTHESIS LOCUS IN MENINGOCOCCAL CARRIAGE AND DISEASE ISOLATES FROM UK Kugelberg Elisabeth 1, Gollan Bridget 1, Farrance Christopher 1, Bratcher Holly 2, Lucidarme Jay 3, Ibarz-Pavon Ana Belen 2, Maiden Martin 2, Borrow Ray 3, Tang Christoph
Conclusions 1
1
Imperial College London, UK 2 University of Oxford, UK 3 Health Protection Agency, Manchester, UK
Introduction The complement system is critical for immunity against the human pathogen Neisseria meningitidis. The current polysaccharide conjugate vaccine against serogroup C N. meningitidis (MenC) has lead to a striking decrease in disease caused by this serogroup. We have previously identified MenC strains, isolated in Spain from invasive cases, which avoid killing by bactericidal antibodies in vaccinees’ sera. These isolates were shown to have an insertion of IS1301 in the intergenic region (IGR) between the operons necessary for capsule biosynthesis and export. Insertion of IS1301 leads to increased amount of polysaccharide capsule and thereby increased protection against complement-mediated killing.
Methods and results PCR and sequencing was used to screen >1500 meningococcal carriage and disease isolates from UK for the presence of IS1301 in the IGR. IS1301 was not found in the IGR of MenC vaccine failures but was frequent among serogroup B N. meningitidis (MenB) isolates. Interestingly IS1301 found in UK MenB isolates all differed from IS1301 0163-4453/$36 doi:10.1016/j.jinf.2010.09.005
MenC disease in UK vaccine failures is not caused by isolates with IS1301 in the IGR. There is no significant difference for the presence of IS1301 in the IGR of MenB disease isolates compared to carriage isolates. IS1301 with associated novel polymorphisms in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.
2 THE VACCINE ANTIGEN FACTOR H BINDING PROTEIN FROM NEISSERIA MENINGITIDIS CAN BE MODIFIED TO REDUCE BINDING TO FACTOR H WITH NO CHANGE IN IMMUNOGENICITY Tan Lionel 1, Caesar Joe 2, Li Yanwen 1, Exley Rachel 1, Kugelberg Elisabeth 1, Zhang Qian 1, Yan Gabriel 1, Lea Susan 2, Tang Christoph 1 1
Centre for Molecular Microbiology & Infection, Imperial College London, UK 2 Sir William Dunn School of Pathology, University of Oxford, UK
Introduction Neisseria meningitidis recruits the negative complement regulator, factor H (fH),to its surface via factor H binding