Molecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus.
The 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODN-adjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN-alpha2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freund's adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations.
Fang
Yuan
Y
Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, People's Republic of China.
Rowe
Thomas
T
Leon
Alberto J
AJ
Banner
David
D
Danesh
Ali
A
Xu
Luoling
L
Ran
Longsi
L
Bosinger
Steven E
SE
Guan
Yi
Y
Chen
Honglin
H
Cameron
Cheryl C
CC
Cameron
Mark J
MJ
Kelvin
David J
DJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005289:Ferrets; D005620:Freund's Adjuvant / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D007370:Interferon Type I / Q000276:immunology; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D007252:Influenza Vaccines; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D005620:Freund's Adjuvant