Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells
AuthorPark, H-Y; Tan, PS; Kavishna, R; Ker, A; Lu, J; Chan, CEZ; Hanson, BJ; MacAry, PA; Caminschi, I; Shortman, K; ...
Source Titlenpj Vaccines
PublisherNATURE PUBLISHING GROUP
AffiliationMedical Biology (W.E.H.I.)
Microbiology and Immunology
Document TypeJournal Article
CitationsPark, 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), https://doi.org/10.1038/s41541-017-0033-5.
Access StatusOpen Access
NHMRC Grant codeNHMRC/1016629
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.
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