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Title: Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells
Authors: Park, H.-Y
Tan, P.S
Kavishna, R 
Ker, A 
Lu, J 
Chan, C.E.Z
Hanson, B.J 
MacAry, P.A 
Caminschi, I
Shortman, K 
Alonso, S 
Lahoud, M.H
Issue Date: 2017
Citation: Park, H.-Y, Tan, P.S, Kavishna, R, Ker, A, Lu, J, Chan, C.E.Z, Hanson, B.J, MacAry, P.A, Caminschi, I, Shortman, K, Alonso, S, Lahoud, M.H (2017). Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells. npj Vaccines 2 (1) : 33. ScholarBank@NUS Repository.
Abstract: Targeting model antigens (Ags) to Clec9A on DC has been shown to induce, not only cytotoxic T cells, but also high levels of Ab. In fact, Ab responses against immunogenic Ag were effectively generated even in the absence of DC-activating adjuvants. Here we tested if targeting weakly immunogenic putative subunit vaccine Ags to Clec9A could enhance Ab responses to a level likely to be protective. The proposed "universal" influenza Ag, M2e and the enterovirus 71 Ag, SP70 were linked to anti-Clec9A Abs and injected into mice. Targeting these Ags to Clec9A greatly increased Ab titres. For optimal responses, a DC-activating adjuvant was required. For optimal responses, a boost injection was also needed, but the high Ab titres against the targeting construct blocked Clec9A-targeted boosting. Heterologous prime-boost strategies avoiding cross-reactivity between the priming and boosting targeting constructs overcame this limitation. In addition, targeting small amounts of Ag to Clec9A served as an efficient priming for a conventional boost with higher levels of untargeted Ag. Using this Clec9A-targeted priming, conventional boosting strategy, M2e immunisation protected mice from infection with lethal doses of influenza H1N1 virus. © 2017 The Author(s).
Source Title: npj Vaccines
ISSN: 20590105
DOI: 10.1038/s41541-017-0033-5
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