Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine
Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
EMBO Press
2020
|
| _version_ | 1797096944213950464 |
|---|---|
| author | O'Connor, D Pinto, MV Sheerin, D Tomic, A Drury, RE Channon-Wells, S Galal, U Dold, C Robinson, H Kerridge, S Plested, E Hughes, H Stockdale, L Sadarangani, M Snape, MD Rollier, CS Levin, M Pollard, AJ |
| author_facet | O'Connor, D Pinto, MV Sheerin, D Tomic, A Drury, RE Channon-Wells, S Galal, U Dold, C Robinson, H Kerridge, S Plested, E Hughes, H Stockdale, L Sadarangani, M Snape, MD Rollier, CS Levin, M Pollard, AJ |
| author_sort | O'Connor, D |
| collection | OXFORD |
| description | Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post‐vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP‐IPV‐Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post‐vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G‐CSF, IL‐1RA and IL‐6. Post‐vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin‐3, ‐5 and GM‐CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine. |
| first_indexed | 2024-03-07T04:48:42Z |
| format | Journal article |
| id | oxford-uuid:d4372b44-09f4-4afb-94b0-d532e147d4a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:48:42Z |
| publishDate | 2020 |
| publisher | EMBO Press |
| record_format | dspace |
| spelling | oxford-uuid:d4372b44-09f4-4afb-94b0-d532e147d4a72022-03-27T08:16:51ZGene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccineJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d4372b44-09f4-4afb-94b0-d532e147d4a7EnglishSymplectic ElementsEMBO Press2020O'Connor, DPinto, MVSheerin, DTomic, ADrury, REChannon-Wells, SGalal, UDold, CRobinson, HKerridge, SPlested, EHughes, HStockdale, LSadarangani, MSnape, MDRollier, CSLevin, MPollard, AJNeisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post‐vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP‐IPV‐Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post‐vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G‐CSF, IL‐1RA and IL‐6. Post‐vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin‐3, ‐5 and GM‐CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine. |
| spellingShingle | O'Connor, D Pinto, MV Sheerin, D Tomic, A Drury, RE Channon-Wells, S Galal, U Dold, C Robinson, H Kerridge, S Plested, E Hughes, H Stockdale, L Sadarangani, M Snape, MD Rollier, CS Levin, M Pollard, AJ Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title | Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title_full | Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title_fullStr | Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title_full_unstemmed | Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title_short | Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine |
| title_sort | gene expression profiling reveals insights into infant immunological and febrile responses to group b meningococcal vaccine |
| work_keys_str_mv | AT oconnord geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT pintomv geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT sheerind geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT tomica geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT druryre geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT channonwellss geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT galalu geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT doldc geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT robinsonh geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT kerridges geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT plestede geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT hughesh geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT stockdalel geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT sadaranganim geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT snapemd geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT rolliercs geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT levinm geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine AT pollardaj geneexpressionprofilingrevealsinsightsintoinfantimmunologicalandfebrileresponsestogroupbmeningococcalvaccine |