Projects per year
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.
Original language | English |
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Article number | 33 |
Number of pages | 11 |
Journal | Vaccines |
Volume | 2 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2017 |
Keywords
- innate immunity
- protein vaccines
Projects
- 2 Finished
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Molecular basis for the efficient processing of antigens taken up by Clec9A, a DAMP receptor on dendritic cells
Lahoud, M., Caminschi, I. & Shortman, K. D.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/19
Project: Research
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Boosting effectiveness of new vaccines for dengue, HFMD and influenza by targeting vaccine antigens to Clec9A on dendritic cells
Lahoud, M. & Shortman, K. D.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/13 → 31/12/15
Project: Research