Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells

Hae-Young Park, Peck S. Tan, Ranmali Kavishna, Anna Ker, Jinhua Lu, Conrad E.Z. Chan, Brendon J. Hanson, Paul A. MacAry, Irina Caminschi, Ken Shortman, Sylvie Alonso, Mireille H. Lahoud

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

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 languageEnglish
Article number33
Number of pages11
Journalnpj Vaccines
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • innate immunity
  • protein vaccines

Cite this

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. / Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells. In: npj Vaccines. 2017 ; Vol. 2, No. 1.
@article{f1e712f7b98e4a4a8ff7e8dbb9c7803b,
title = "Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells",
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.",
keywords = "innate immunity, protein vaccines",
author = "Hae-Young Park and Tan, {Peck S.} and Ranmali Kavishna and Anna Ker and Jinhua Lu and Chan, {Conrad E.Z.} and Hanson, {Brendon J.} and MacAry, {Paul A.} and Irina Caminschi and Ken Shortman and Sylvie Alonso and Lahoud, {Mireille H.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41541-017-0033-5",
language = "English",
volume = "2",
journal = "Vaccines",
issn = "2076-393X",
publisher = "MDPI",
number = "1",

}

Park, H-Y, Tan, PS, Kavishna, R, Ker, A, Lu, J, Chan, CEZ, Hanson, BJ, MacAry, PA, Caminschi, I, Shortman, K, Alonso, S & Lahoud, MH 2017, 'Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells', npj Vaccines, vol. 2, no. 1, 33. https://doi.org/10.1038/s41541-017-0033-5

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 journalArticleResearchpeer-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 -