Langerin negative dendritic cells promote potent CD8
            <sup>+</sup>
            T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

Bachy, Véronique; Hervouet, Catherine; Becker, Pablo D.; Chorro, Laurent; Carlin, Leo M.; Herath, Shan; Papagatsias, Timos; Barbaroux, Jean Baptiste; Oh, Sea Jin; Benlahrech, Adel; Athanasopoulos, Takis; Dickson, George; Patterson, Steven; Kwon, Sung Yun; Geissmann, Frédéric; Klavinskis, Linda

doi:10.1073/pnas.1214449110

Cited by 83 publications

(91 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recombinant adenovirus type 5 (rAdHu5) vectors encoding codon optimized HIV-1 Gag from ConsB, strain 96ZM651.8 (ZM96) and strain 97CN54 (CN54) (43), are described in SI Appendix, SI Materials and Methods.…”

Section: Application Of Ann-hydro For Each H-2dmentioning

confidence: 99%

“…Spleen cells were restimulated either with media alone or with peptides, either in pools or individually (each at 1 μM final concentration), and IFN-γ production was detected by intracellular cytokine staining or by ELISPOT assay as described previously (43). ConsB and CN54 Gag epitopes were deconvoluted to individual 15 mers from peptide pools, and truncated versions of the 15-mer peptides were synthesized and tested.…”

Section: Application Of Ann-hydro For Each H-2dmentioning

confidence: 99%

See 1 more Smart Citation

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes

Chowell

Krishna

Becker

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

209

207

View full text Add to dashboard Cite

Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8+ T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.

show abstract

Section: Application Of Ann-hydro For Each H-2dmentioning

confidence: 99%

Section: Application Of Ann-hydro For Each H-2dmentioning

confidence: 99%

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes

Chowell

Krishna

Becker

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

209

207

View full text Add to dashboard Cite

show abstract

“…The thinner and shorter microneedle (1.5 mm in length) reduces pain significantly. The pain may be further reduced by a microneedle array (MNs) or a patch where each array contains hundreds or thousands of tiny microneedles (12)(13)(14)(15). To load a sufficient amount of vaccine in a patch, these microneedles are usually densely packed in a small patch (∼1 cm 2 ).…”

mentioning

confidence: 99%

Effective and lesion-free cutaneous influenza vaccination

Wang

2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigenuptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other "danger" signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies.biodegradable microneedle | nonablative fractional laser | dsDNA S ubstantial evidence has shown that skin is a more potent site for vaccination than muscle because the former contains a large number of antigen presenting cells (APCs) and abundant network of lymphatic vessels. Moreover, skin offers potential for painless, needle-free, and self-applicable immunization, which would particularly benefit annual influenza vaccination of large populations (1, 2). However, skin immunization has not been broadly adopted to date, due to lack of safe adjuvants and technical difficulties in injecting vaccines into the ultrathin (<2 mm) skin tissue (3,4). We have demonstrated that controllable skin injury can serve as safe "adjuvant" for cutaneous vaccination and similar observations have been also made by other investigators (5-7). Treatment of the inoculation site with nonablative fractional laser (NAFL) generates an array of microthermal zones (MTZs) beneath the stratum corneum (8). The dying cells in the MTZs release "danger" signals that provoke sterile inflammation that is however constrained within individual MTZs. This array of microsterile inflammatory zones is resolved quickly, effectively averting skin lesion, provided that affected and unaffected areas of the skin are adequately balanced (8). Importantly, despite fast resolution, the microinflammation zones prove sufficient in augmentation of adaptive immune responses against the vaccine (5). In addition, this standalone adjuvant does not affect the volume of administration or formulation of the vaccine, which are serious hurdles for...

show abstract

“…20,[29][30][31] The stability of inactivated viruses and protein antigens has been established in certain dissolvable microneedle formulations [32][33][34] however, little investigation has been done to determine whether incorporation into dissolvable microneedles has any influence on the stability of DNA or to directly compare the suitability of different polymer matrices to deliver nucleic acid cargo. This is perhaps surprising given that some polymers have been known to form hydrogen bonds with DNA and have been reported to be capable of enhancing gene delivery in their own right.…”

Section: Introductionmentioning

confidence: 99%

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Cole

McCaffrey

Ali

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.

show abstract

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

Cited by 83 publications

References 28 publications

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes

Effective and lesion-free cutaneous influenza vaccination

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Contact Info

Product

Resources

About

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

Cited by 83 publications

References 28 publications

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+T cell epitopes

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+T cell epitopes

Effective and lesion-free cutaneous influenza vaccination

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Contact Info

Product

Resources

About

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

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8⁺T cell epitopes