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Abstract
Cell mediated immunity plays a vital role in defense against influenza infection in humans. Less is known about the role of vaccine-induced cell mediated immunity and the cytokine responses elicited. We measured CD4+ and CD8+ T-cell reactivity in human subjects following vaccination with licensed trivalent influenza vaccine and a novel virus-like particle based vaccine. We detected influenza-specific CD4+ T-cell responses following vaccination with the licensed trivalent influenza vaccine and found that these correlated with antibody measurements. Administration of the novel virus-like particle based vaccine elicited influenza-specific CD4+ and CD8+ T-cell responses and the induction of the cytokines IFN-γ, IL-17A, IL17F, IL-5, IL-13, IL-9, IL-10 and IL-21. Pre-existing cytokine responses influenced the profile of the cytokine response elicited by vaccination. In a subset of individuals the VLP vaccine changed pre-vaccination production of type 2 cytokines such as IL-5 and IL-13 to a post-vaccination type 1 cytokine signature characterized by IFN-γ. A transcriptional signature to vaccination was found to correlate with antibody titer, IFN-γ production by T-cells and expression of a putative RNA helicase, DDX17, on the surface of immune cells.
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1 Institute of Molecular and Cell Biology, Singapore, Singapore; A*STAR Program in Translational Research on Infectious Disease, Agency for Science, Technology and Research, Singapore, Singapore
2 Institute of Molecular and Cell Biology, Singapore, Singapore
3 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
4 Singapore Immunology Network (SIgN), 8A Biomedical Grove, Immunos Bldg, Singapore, Singapore
5 SingHealth Investigational Medicine Unit, Singapore General Hospital, Singapore, Singapore; Singapore General Hospital, Singapore, Singapore
6 Clinical Trials Research Unit, Changi General Hospital, Singapore, Singapore; National University of Singapore, Department of Medicine, Singapore, Singapore
7 Cytos Biotechnology AG, Zürich-Schlieren, Switzerland
8 Inselspital, RIA, Immunologie, Bern, Switzerland
9 Duke-NUS Medical School, Program in Emerging Infectious Diseases, Singapore, Singapore
10 DSO National Laboratories, Bio-Defense Therapeutics Lab, Singapore, Singapore
11 D3 (Drug Discovery and Development), Singapore, Singapore
12 Institute of Molecular and Cell Biology, Singapore, Singapore; A*STAR Program in Translational Research on Infectious Disease, Agency for Science, Technology and Research, Singapore, Singapore; Institute of Biomedical Studies, Baylor University, Waco, Texas, USA