Langerin negative dendritic cells promote potent CD8(+) T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

TY - JOUR

T1 - Langerin negative dendritic cells promote potent CD8(+) T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

AU - Bachy, Veronique

AU - Hervouet, Catherine

AU - Becker, Pablo D.

AU - Chorro, Laurent

AU - Carlin, Leo M.

AU - Herath, Shanthi

AU - Papagatsias, Timos

AU - Barbaroux, Jean-Baptiste

AU - Oh, Sea-Jin

AU - Benlahrech, Adel

AU - Athanasopoulos, Takis

AU - Dickson, George

AU - Patterson, Steven

AU - Kwon, Sung-Yun

AU - Geissmann, Frederic

AU - Klavinskis, Linda S.

PY - 2013/2/19

Y1 - 2013/2/19

N2 - Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCIIhi CD8 alpha(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCswere required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.

AB - Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCIIhi CD8 alpha(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCswere required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.

KW - MUCOSAL

KW - IMMUNITY

KW - ACQUISITION

KW - IMMUNIZATION

KW - ANTIGENS

KW - SIV

KW - INFECTION

KW - IN-VIVO

KW - COMPLEXES

KW - CHALLENGES

U2 - 10.1073/pnas.1214449110

DO - 10.1073/pnas.1214449110

M3 - Article

C2 - 23386724

SN - 1091-6490

VL - 110

SP - 3041

EP - 3046

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 8

ER -