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

ReferencesCenters 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