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Type: Journal article
Title: Viral vector and route of administration determine the ILC and DC profiles responsible for downstream vaccine-specific immune outcomes
Author: Roy, S.
Jaeson, M.
Li, Z.
Mahboob, S.
Jackson, R.
Grubor-Bauk, B.
Wijesundara, D.
Gowans, E.
Ranasinghe, C.
Citation: Vaccine, 2019; 37(10):1266-1276
Publisher: Elsevier
Issue Date: 2019
ISSN: 0264-410X
Statement of
S. Roy, M.I. Jaeson, Z. Li, S. Mahboob, R.J. Jackson, B. Grubor-Bauk, D.K. Wijesundara, E.J. Gowans, C. Ranasinghe
Abstract: This study demonstrates that route and viral vector can significantly influence the innate lymphoid cells (ILC) and dendritic cells (DC) recruited to the vaccination site, 24 h post delivery. Intranasal (i.n.) vaccination induced ST2/IL-33R+ ILC2, whilst intramuscular (i.m.) induced IL-25R+ and TSLPR+ (Thymic stromal lymphopoietin protein receptor) ILC2 subsets. However, in muscle a novel ILC subset devoid of the known ILC2 markers (IL-25R- IL-33R- TSLPR-) were found to express IL-13, unlike in lung. Different viral vectors also influenced the ILC-derived cytokines and the DC profiles at the respective vaccination sites. Both i.n. and i.m. recombinant fowlpox virus (rFPV) priming, which has been associated with induction of high avidity T cells and effective antibody differentiation exhibited low ILC2-derived IL-13, high NKp46+ ILC1/ILC3 derived IFN-γ and low IL-17A, together with enhanced CD11b+ CD103- conventional DCs (cDC). In contrast, recombinant Modified Vaccinia Ankara (rMVA) and Influenza A vector priming, which has been linked to low avidity T cells, induced opposing ILC derived-cytokine profiles and enhanced cross-presenting DCs. These observations suggested that the former ILC/DC profiles could be a predictor of a balanced cellular and humoral immune outcome. In addition, following i.n. delivery Rhinovirus (RV) and Adenovius type 5 (Ad5) vectors that induced elevated ILC2-derived IL-13, NKp46+ ILC1/ILC3-derived-IFN-γ and no IL-17A, predominantly recruited CD11b- B220+ plasmacytoid DCs (pDC). Knowing that pDC are involved in antibody differentiation, we postulate that i.n. priming with these vectors may favour induction of effective humoral immunity. Our data also revealed that vector-specific replication status and/or presence or absence of immune evasive genes can significantly alter the ILC and DC activity. Collectively, our findings suggest that understanding the route- and vector-specific ILC and DC profiles at the vaccination site may help tailor/design more efficacious viral vector-based vaccines, according to the pathogen of interest.
Keywords: DC
Mucosal and systemic vaccination
Viral vector-based vaccines
Rights: © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CCBY-NC-NDlicense ( ).
DOI: 10.1016/j.vaccine.2019.01.045
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