System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep.

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State: Public
Version: Final published version
Serval ID
serval:BIB_2505CAFEEAF3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep.
Journal
NPJ vaccines
Author(s)
Braun R.O., Brunner L., Wyler K., Auray G., García-Nicolás O., Python S., Zumkehr B., Gaschen V., Stoffel M.H., Collin N., Barnier-Quer C., Bruggmann R., Summerfield A.
ISSN
2059-0105 (Electronic)
ISSN-L
2059-0105
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
3
Pages
41
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Inactivated vaccines lack immunogenicity and therefore require potent adjuvants. To understand the in vivo effects of adjuvants, we used a system immunology-based analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune responses relating to either antibody or haptoglobin levels. Using inactivated foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands. Early after vaccination, BTM relating to myeloid cells, innate immune responses, dendritic cells, and antigen presentation correlated positively, whereas BTM relating to T and natural killer cells, as well as cell cycle correlated negatively with antibody responses. Interestingly, similar BTM also correlated with haptoglobin, but in a reversed manner, indicating that acute systemic inflammation is not beneficial for early antibody responses. Analysis of vaccine-dependent BTM modulation showed that liposomal formulations induced similar responses to those correlating to antibody levels. Surprisingly, the addition of the TLR ligands appeared to reduce early immunological perturbations and mediated anti-inflammatory effects, despite promoting antibody responses. When pre-vaccination BTM were analyzed, we found that high vaccine responders expressed higher levels of many BTM relating to cell cycle, antigen-presenting cells, and innate responses as compared with low responders. In conclusion, we have transferred human BTM to sheep and identified early vaccine-induced responses associated with antibody levels or unwanted inflammation in a heterogeneous and small group of animals. Such readouts are applicable to other veterinary species and very useful to identify efficient vaccine adjuvants, their mechanism of action, and factors related to low responders.
Pubmed
Web of science
Open Access
Yes
Create date
22/10/2018 16:24
Last modification date
20/08/2019 13:03
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