![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Live attenuated influenza vaccines (LAIV) can prevent influenza illness and death in children. The absence of known correlates of protection induced by LAIV requires human studies of underlying mechanisms of vaccine-induced immunity, to further elucidate the immunological processes occurring. In this study, children scheduled for elective tonsillectomy were enrolled in a clinical trial to evaluate the immune response to LAIV, in order to compare T and B cell gene expression profiles. Twenty-three children (aged 3–17 years) were divided into 4 groups; unvaccinated controls, or vaccinated intranasally with LAIV at days 3–4, 6–7, and 12–15 before tonsillectomy. Total RNA extraction was performed on tonsillar tissue and high RNA quality was assured. The samples were then analyzed using a validated RT2 Profiler PCR Array containing 84 gene-specific primers involved in B and T cell activation, proliferation, differentiation, regulation and polarization. The gene expression after LAIV vaccination was subsequently compared to the controls. We observed that at d 3–4 post vaccination, 6 genes were down-regulated, namely APC, CD3G, FASLG, IL7, CD8A and TLR1. Meanwhile at 6–7 days post vaccination, 9 genes were significantly up-regulated, including RIPK2, TGFB1, MICB, SOCS1, IL2RA, MS4A1, PTPRC, IL2 and IL8. By days 12–15 the genes RIPK2, IL4, IL12B and TLR2 were overexpressed. RIPK2 was upregulated at all 3 time points. Our data suggests an overall proliferation, differentiation and regulation of B and T cells in the tonsils following LAIV, where the majority of genes were up-regulated at days 6–7 and normalized by days 12–15. These findings may provide a first step into defining future biomarkers or correlates of protection after LAIV immunization.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We express our gratitude to the children who underwent tonsillectomy and their supportive parents, who altruistically joined our clinical trial. Their collaboration has been essential for the accomplishment of the study presented. We thank Dr. Hans J. Aarstad at the Ear, Nose and Throat division, Dr. Camilla Tøndel and the nurses at the Children Trial Unit, Haukeland University Hospital, for their help and collaboration, the laboratory staff at the Influenza Center, Gina Bergh and Kjerstin Jakobsen at the Broegelmann Research Laboratory, for excellent technical assistance. Finally, we would like to thank Professor Karl-Henning Kalland at the Department of Clinical Science for the valuable scientific discussions.
Funding
The Influenza Center is funded by the Ministry of Health and Care Services, Norway, the Norwegian Research Council Globvac program (220670/H10), the European Union (Univax 601738) and (EU IMI, FLUCOP 115672), Helse Vest and the K.G. Jebsen Center for Influenza Vaccines.
Supplemental Material
Supplemental data for this article can be accessed on the publisher's website.