Influenza is a major cause of morbidity and mortality worldwide. Although vaccination is the most effective Strategy to prevent infection, influenza vaccination coverage is insufficient and improved vaccine immunogenicity is needed. We propose development of a microneedle patch that is simple enough to increase vaccination coverage by enabling self-administration and specifically designed to improve immunogenicity by targeting dendritic cells in skin. Microneedles (MN) are micron-scale, solid needles that administer vaccine directly into skin using a simple, painless and minimally invasive approach. The patch is designed to enable skin vaccination with a patch application time of just seconds, generation of no sharp biohazardous waste, and antigen stability during storage without refrigeration. The goal of this milestone-driven project is to develop a MN patch for influenza vaccination and assess its safety and immunogenicity in a Phase I clinical trial.
In Aim 1, based at Georgia Tech, we will design, formulate, and fabricate MN for simple, rapid application and long-term stability.
In Aim 2, based at Emory, we will assess MN vaccination in three animal models with the goals of validating suitability for human trials and enhancing immunogenicity.
Aim 3 will be achieved with external contractors and consultants to develop and validate cGMP manufacturing, conduct GLP preclinical studies and obtain an IND. This work will culminate in a Phase I clinical trial carried out in Aim 4 at Emory's Hope Clinic to assess safety, tolerability, immunogenicity and acceptability of influenza vaccination using a MN patch. Finally, Aim 5 will be based at PATH to assess regulatory, cost and policy issues associated with self-administered influenza vaccination. Expected outcomes from this research are (i) development of a low-cost MN patch that administers influenza vaccine in a simple, rapid manner, (ii) identification of immunologic differences and advantages of MN-based influenza vaccination compared to IM vaccination that will be used to improve the MN patch, (iii) production of MN patches for influenza vaccination under cGMP and IND approval from FDA, (iv) completion of a Phase I clinical trial assessing safety, tolerability, immunogenicity and acceptability of influenza vaccination using MN and (v) identification of regulatory, cost and policy issues to guide development and future introduction of our MN patch into clinical practice. These outcomes not only impact influenza vaccination, but also provide a basis for delivery of other vaccines and drugs using MN patches.
Despite annual influenza vaccination campaigns, CDC attributes 36,000 deaths and 226,000 hospitalizations per year in the US to influenza, with an associated cost of ~$100 billion per year. As a quantum advance, this project will develop a novel microneedle patch designed to increase vaccination coverage by enabling simple, self-vaccination and increase vaccine immunogenicity by targeting antigen delivery to skin. The proposed Phase I clinical trial will provide the first human study of this technology.
|Arya, Jaya; Henry, Sebastien; Kalluri, Haripriya et al. (2017) Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects. Biomaterials 128:1-7|
|Rouphael, Nadine G; Paine, Michele; Mosley, Regina et al. (2017) The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Lancet 390:649-658|
|Mistilis, Matthew J; Joyce, Jessica C; Esser, E Stein et al. (2017) Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv Transl Res 7:195-205|
|Chu, Leonard Y; Ye, Ling; Dong, Ke et al. (2016) Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches. Pharm Res 33:868-78|
|Arya, Jaya; Prausnitz, Mark R (2016) Microneedle patches for vaccination in developing countries. J Control Release 240:135-141|
|Mistilis, Matthew J; Bommarius, Andreas S; Prausnitz, Mark R (2015) Development of a thermostable microneedle patch for influenza vaccination. J Pharm Sci 104:740-9|
|Jacoby, Erica; Jarrahian, Courtney; Hull, Harry F et al. (2015) Opportunities and challenges in delivering influenza vaccine by microneedle patch. Vaccine 33:4699-704|
|Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R et al. (2015) Enhanced immune responses by skin vaccination with influenza subunit vaccine in young hosts. Vaccine 33:4675-82|
|Choi, Hyo-Jick; Song, Jae-Min; Bondy, Brian J et al. (2015) Effect of Osmotic Pressure on the Stability of Whole Inactivated Influenza Vaccine for Coating on Microneedles. PLoS One 10:e0134431|
|Vassilieva, Elena V; Kalluri, Haripriya; McAllister, Devin et al. (2015) Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature. Drug Deliv Transl Res 5:360-71|
Showing the most recent 10 out of 36 publications