Skin vaccination with live virus vectored microneedle arrays induce long lived CD8(+) T cell memory.
A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. While recent studies have focused largely on design parameters optimized to induce primary CD8(+) T cell responses, the hallmark of a vaccine is synonymous with engendering long-lasting memory. Here, we address the capacity of dried MA vaccination to programme phenotypic markers indicative of effector/memory CD8(+) T cell subsets and also responsiveness to recall antigen benchmarked against conventional intradermal (ID) injection. We show that despite a slightly lower frequency of dividing T cell receptor transgenic CD8(+) T cells in secondary lymphoid tissue at an early time point, the absolute number of CD8(+) T cells expressing an effector memory (CD62L(-)CD127(+)) and central memory (CD62L(+)CD127(+)) phenotype during peak expansion were comparable after MA and ID vaccination with a recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. Similarly, both vaccination routes generated CD8(+) memory T cell subsets detected in draining LNs for at least two years post-vaccination capable of responding to secondary antigen. These data suggest that CD8(+) T cell effector/memory generation and long-term memory is largely unaffected by physical differences in vaccine delivery to the skin via dried MA or ID suspension.
Peter Gorer Department of Immunobiology, Faculty of Life Sciences and Medicine, Kings's College London, London SE1 9RT, United Kingdom. Electronic address: pablo.becker@kcl.ac.uk.
Pablo D
PD
Becker
Peter Gorer Department of Immunobiology, Faculty of Life Sciences and Medicine, Kings's College London, London SE1 9RT, United Kingdom. Electronic address: Catherine.hervouet@unice.fr.
Catherine
C
Hervouet
Peter Gorer Department of Immunobiology, Faculty of Life Sciences and Medicine, Kings's College London, London SE1 9RT, United Kingdom. Electronic address: gavin.mason@kcl.ac.uk.
Gavin M
GM
Mason
TheraJect Inc., Fremont, CA 94538, United States. Electronic address: sykwon@theraject.com.
Sung-Yun
SY
Kwon
Peter Gorer Department of Immunobiology, Faculty of Life Sciences and Medicine, Kings's College London, London SE1 9RT, United Kingdom. Electronic address: linda.klavinskis@kcl.ac.uk.
Linda S
LS
Klavinskis
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016503:Drug Delivery Systems; D007156:Immunologic Memory; D007271:Injections, Intradermal; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage
D016915:AIDS Vaccines; D014614:Vaccines, Synthetic
Adenovirus vector; CD8(+) T cell; Memory; Microneedle array; Skin immunization