Microneedle Delivery of H5N1 Influenza Virus-Like Particles to the Skin Induces Long-Lasting B- and T-Cell Responses in Mice

Song, June O.; Kim, Yeu‐Chun; Lipatov, A. S.; Pearton, Marc; Davis, C. Todd; Yoo, Dae-Goon; Park, Kyoung Mi; Chen, Limei; Quan, Fu‐Shi; Birchall, James Caradoc; Donis, Ruben O.; Prausnitz, Mark R.; Compans, Richard W.; Kang, Sang‐Moo

doi:10.1128/cvi.00100-10

Cited by 67 publications

(46 citation statements)

References 54 publications

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“…The other three strata of the epidermis (S. granulosum, S. spinosum and S. basale) all contain ketatinocytes at different stages of differentiation as well as the immune Langerhans cells and dermal dendritic cells. [11][12][13] Both physical and chemical methods for transdermal drug delivery and gene delivery have been detailed by groups worldwide. Iontophoresis, lipid delivery and gene gun are such examples.…”

Section: Introductionmentioning

confidence: 99%

Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device

et al. 2010

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The magnitude of the immune response to a DNA vaccine depends on three criteria-the optimized vector design, the use of a suitable adjuvant and the successful delivery and subsequent expression of the plasmid in the target tissue. In vivo electroporation (EP) has proved to be particularly effective in efficiently delivering DNA immunogens to the muscle and the skin, and indeed several devices have entered into human clinical trials. Here, we report on a novel concept of DNA delivery to the dermal tissue using a minimally invasive EP device, which is powered using low-voltage parameters. We show that this prototype device containing a novel 4Â4-electrode array results in robust and reproducible transfection of dermal tissue and subsequent antigen expression at the injection site. Using DNA encoding for NP and M2e influenza antigens, we further show induction of potent cellular responses in a mouse model as measured by antigen-specific T-cell ELISpot assays. Importantly, 100% of the immunized animals were protected when challenged with VN/1203/04 (H5N1) strain of influenza. We have also extended our findings to a guinea-pig model and demonstrated induction of HI titers greater than 1:40 against a pandemic novel H1N1 virus showing proof of concept efficacy for DNA delivery with the prototype device in a broad spectrum of species and using multiple antigens. Finally, we were able to generate protective HI titers in macaques against the same novel H1N1 strain. Our results suggest that the minimally invasive dermal device may offer a safe, tolerable and efficient method to administer DNA vaccinations in a prophylactic setting, and thus potentially represents an important new option for improved DNA vaccine delivery in vivo.

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Section: Introductionmentioning

confidence: 99%

Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device

et al. 2010

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“…Different types of microneedle influenza vaccines and efficacies have been demonstrated. Substantial amounts of viral loads with a range of 10 4 -to 10 5 -PFU titers were detected in mice that were immunized on the skin using microneedles coated with 0.4 to 2 g H5 HA VLPs derived from influenza A/Vietnam/1203/04 virus (21,35). Also, 10 2 -to 10 3 -PFU lung viral titers and weight losses of 5 to 10% were observed in mice immunized with microneedle vaccines coated with 3 g of split A/Brisbane/59/2007 vaccine, which are approximately 10-to 50-fold less than the infected naive control group (36).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Protective Immunity from an Influenza Virus-Like Particle Vaccine Administered with a Microneedle Patch

Quan

Kim

Song

et al. 2013

Clin Vaccine Immunol

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f Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

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“…Using similar strategies, Song et al proved that H5N1 avian influenza VLP-constituted MAs induced long-lasting B-and T-cell responses with improved protection in mice. 74,75 Also, Pearton et al found that influenza VLP-based MAs could initiate a stimulatory response in Langerhans cells (LCs) through deposition of the vaccine in human skin. 12 And further exploration of the complex molecular and cellular host responses to influenza VLP MAs revealed up-regulation of a host of genes responsible for key immunomodulatory processes and host viral response following microneedle injection of VLPs.…”

Section: Influenza Vlp Vaccine Constituted Mpmasmentioning

confidence: 99%

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

Wang

et al. 2016

Human Vaccines & Immunotherapeutics

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To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by selfadministration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS).

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Microneedle Delivery of H5N1 Influenza Virus-Like Particles to the Skin Induces Long-Lasting B- and T-Cell Responses in Mice

Cited by 67 publications

References 54 publications

Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device

Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device

Long-Term Protective Immunity from an Influenza Virus-Like Particle Vaccine Administered with a Microneedle Patch

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

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