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 |
|---|---|
| Article number | 33 |
| Number of pages | 11 |
| Journal | npj Vaccines |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
Keywords
- innate immunity
- protein vaccines
Cite this
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Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells. / Park, Hae-Young; Tan, Peck S.; Kavishna, Ranmali; Ker, Anna; Lu, Jinhua; Chan, Conrad E.Z.; Hanson, Brendon J.; MacAry, Paul A.; Caminschi, Irina; Shortman, Ken; Alonso, Sylvie; Lahoud, Mireille H.
In: npj Vaccines, Vol. 2, No. 1, 33, 01.12.2017.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells
AU - Park, Hae-Young
AU - Tan, Peck S.
AU - Kavishna, Ranmali
AU - Ker, Anna
AU - Lu, Jinhua
AU - Chan, Conrad E.Z.
AU - Hanson, Brendon J.
AU - MacAry, Paul A.
AU - Caminschi, Irina
AU - Shortman, Ken
AU - Alonso, Sylvie
AU - Lahoud, Mireille H.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - innate immunity
KW - protein vaccines
UR - http://www.scopus.com/inward/record.url?scp=85042210688&partnerID=8YFLogxK
U2 - 10.1038/s41541-017-0033-5
DO - 10.1038/s41541-017-0033-5
M3 - Article
VL - 2
JO - Vaccines
JF - Vaccines
SN - 2076-393X
IS - 1
M1 - 33
ER -