A genomics-based approach to assessment of vaccine safety and immunogenicity in children.
Immune responses to vaccines in infants and young children are typically Th2-biased, giving rise to concerns regarding potential atopy-like side effects, and antagonism of Th1-associated sterilising immunity. Conventional immunological methodology has limited capacity to effectively address these problems because of the inherent complexity of the immune responses involved. In the present study, we sought to develop an unbiased systems biology approach to elucidate superficially similar Th2-associated responses to paediatric vaccines and allergens, and to differentiate between them via gene coexpression network analysis. We demonstrate below that in immune responses to the diptheria/acellular pertussis/tetanus and pneumococcal polysaccharide conjugate vaccines, potentially antagonistic Th1-/IFN-associated and Th2-associated gene networks coexist in an apparent state of dynamic equilibrium, whereas in Th2-dominant allergen-specific responses of atopics the Th1 and IFN networks are respectively disrupted and downregulated. Capacity to detect and interpret these covert differences between responses to vaccines and allergens relies on the use of sophisticated algorithms that underpin coexpression network analysis, which identify genes that function co-ordinately in complex pathways. This methodology has significant potential to identify covert interactions between inflammatory pathways triggered by vaccination, and as such may be a useful tool in prediction of vaccine safety/efficacy.
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Australia.
Olivia J
OJ
White
Katherine L
KL
McKenna
Anthony
A
Bosco
Anita
A
H J van den Biggelaar
Peter
P
Richmond
Patrick G
PG
Holt
D000293:Adolescent; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000009:adverse effects / Q000276:immunology*; D053263:Gene Regulatory Networks; D023281:Genomics; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007156:Immunologic Memory; D007223:Infant; D020411:Oligonucleotide Array Sequence Analysis; D022242:Pneumococcal Vaccines / Q000009:adverse effects / Q000276:immunology*; D049490:Systems Biology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology
D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate