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Inactivated Influenza Vaccine Administration via Microneedle Patch; a Novel Vaccine Delivery
System
Karen Mask, RN, BSNMPH CandidateApril 11, 2014
Background
Seasonal influenza leads to significant morbidity & mortality each year.
Worldwide: 3 to 5 million cases of severe illness 250,000 to 500,000 deaths per year (WHO, 2009)
United States: >220,000 hospitalizations 36,000 deaths per year (Thompson, 2004)
Vaccination is the most effective way of preventing influenza.
CDC recommends annual flu vaccine for everyone 6 months and older
Background
Despite recommendations, early season vaccination coverage was only 39.5% for 2013-2014 flu season (CDC, 2013)
http://www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm
Background
Barriers to flu vaccination Needle phobia Access to vaccine Vaccine acceptability Need for trained personnel to administer vaccine Lack of financial and physical space resources
Background
Microneedle patches Micron-scale (10-6 m) needles, minimally invasive,
eliminate sharps waste, painless
http://drugdelivery.chbe.gatech.edu/gallery_microneedles.html
Background
Microneedle patch product administration
http://drugdelivery.chbe.gatech.edu/Images/Image_gallery/Full/patch-application.jpg
Background
Microneedle patch pre-clinical studies Mice model microneedle study (Zhu et al, 2009)
Vaccinated with H1N1 and H3N2 strains via microneedle patch
Protected when challenged with lethal flu dose Rabies, BCG, HPV vaccine studies Favorable safety profile to date Acceptability study (Norman et al, 2014)
increased intent to vaccinate with microneedle patches (from 44% to 65%)
majority preference to self-vaccinate (64%)
Rationale
Flu vaccination is highly effective in preventing disease but barriers to vaccination limit the protective impact of influenza vaccination programs.
Microneedle patch delivery system has potential to greatly impact acceptability and ease of delivery of inactivated flu vaccine.
Painless, simple administration Effect more profound in pandemic flu situation Potential to expand beyond influenza vaccine.
Reduction in influenza related morbidity & mortality
Internship
The Hope Clinic of the Emory Vaccine Center; Emory University
National Institutes of Health (NIH) funded Vaccine Treatment and Evaluation Unit (VTEU)
Preceptor – Dr. Nadine Rouphael
Assistant ProfessorDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine
Special Project
A Phase I Study of the Safety, Reactogenicity, Acceptability and Immunogenicity of Inactivated Influenza Vaccine Delivered by Microneedle Patch or by Hypodermic Needle (working title - in development)
Microneedle technology – Dr. Mark Prausnitz
Clinical trial development and execution – Drs. Nadine Rouphael and Mark Mulligan Sponsored by: National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Objectives
Project Development Establish collaborative working group Microneedle team develop concept Clinical team develop clinical trial protocol Secure Investigational New Drug (IND) approval Secure Institutional Review Board (IRB) approvals Complete clinical trial preparation
Clinical Trial Evaluate safety and reactogenicity of study product Evaluate immunogenicity of study product Compare immunogenicity of staff vs. self administration
Methods
Literature search Morbidity & mortality of influenza, microneedle
development and testing, public health programs and roadblocks
CDC Ecological Framework Individual factors (needle phobia) Relationship factors (family members decline vaccine) Community factors (herd immunity) Societal factors (policy)
Policy analysis Vaccination recommendations vs. requirements
Methods
Financial management Grant funding coverage and restrictions
Program planning & evaluation Clinical trial design: subject recruitment, blinding,
statistical significance Results analysis – safety, reactogenicity, immunogenicity
Results
Established collaborative working group Microneedle development team at Georgia Tech led by
Dr. Mark Prausnitz Clinical trial development team at Emory University led
by Dr. Nadine Rouphael Team conference calls and in-person development
meetings Microneedle patch concept developed by Georgia
Tech Delivered to Emory University for study protocol
development
Results
Emory clinical trial team developed draft study design and protocol
Delivered to Georgia Tech for review and pre-IND submission
Progress towards securing IND / IRB approvals Pre-IND meeting held; study team incorporating FDA
comments in protocol and preparing FDA response Working on final IND submissions
Complete clinical trial preparation – Fall 2014/Spring 2015
Clinical trial – Spring/Summer 2015
Results - Timeline
Pre-June 2013 Winter 2015Spring 2015Summer 2014 Fall 2014Summer 2013 Spring 2014
Concept Development
Protocol Development
IND Application
Clinic Preparations
Clinical Trial
Collaborative Group
Discussion
Microneedle technology is very early in development A project of this scope takes several years to
develop, implement and analyze the results Front end of the project is primarily administrative,
but critical to achieving accurate, reliable, and generalizable data
As a first-in-humans trial, this protocol will need to be replicated and/or expanded to ensure results are accurate and generalizable.
Implications
Improved acceptability of annual influenza vaccination
Pain reduction, improved access to vaccine, potential for self-vaccination
Increased compliance to annual influenza vaccination recommendations
Potential decreased influenza morbidity and mortality through improved immunogenicity of intradermal vaccination
Targets antigen-presenting Langerhans and dermal dendritic cells.
Implications
Potential for improved and expanded global vaccination program (provided methods are generalizable to other vaccines)
Improved access to vaccine Improved vaccine stability and less stringent cold chain
requirements Decreased reliance on administration by trained personnel Increased acceptability
Expansion of collaborative partnerships across concentration areas such as engineering and healthcare
MPH Core Competencies Strengthened
Monitoring health status to identify and solve community health problems
Mobilizing community partnerships and action to identify and solve health problems
Evaluating effectiveness, accessibility and quality of personal and population-based health services
Conducting research for new insights and innovative solutions to health problems
Concentration Competencies Strengthened
Identify & understand the historical context of epidemiology, epidemiologic terminology, study designs & methodology
Demonstrate communication skills key to public health workforce participation and advocacy
Effectively manage public health programs and projects
Demonstrate the principles of problem solving and crisis management
Lessons Learned
Challenges associated with Intellectual Property Challenges in collaborative partnerships
between academic institutions Research funding environment Interactions with governmental agencies and
regulatory consultant groups
Thank You
Dr. Nadine Rouphael – Emory University The clinical research team at the Hope Clinic of the
Emory Vaccine Center. Dr. Mark Prausnitz and the microneedle
development team at the Georgia Institute of Technology
Dr. John Lednicky – University of Florida
References
Centers for Disease Control and Prevention. (2013). National early season flu vaccination coverage, United States. Retrieved March 30, 2014 from http://www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm
Norman, J.J., Arya, J.M., McClain, M.A., Frew, P.M., Meltzer, M.I., & Prausnitz, M.R. (2014). Microneedle patches: Usability and acceptability for self-vaccination against influenza. Vaccine, 32(16), 1856-1862.
Thompson, W.W. (2004). Influenza-associated hospitalizations in the United States. Journal of the American Medical Association, 292(11), 1333-1340.
World Health Organization. (2009, April). Influenza (Seasonal). WHO Fact Sheet, 211.
Zhu, Q., Zarnitsyn, V.G., Ye, L., Wen, Z, Gao, Y., Pan, L., Skountzou, I., et al. (2009). Immunization by vaccine-coated microneedle arrays protects against lethal influenza challenge. Proceedings of the National
Academy of Sciences of the United States of America, 106(19), 7968- 7973.
Questions
http://drugdelivery.chbe.gatech.edu/Images/Image_gallery/Full/microneedle-patch2.jpg