The production and distribution of influenza vaccines as well as delivery by medical personnel is extremely time consuming, as seen during the prolonged and inefficient annual vaccination campaigns. To expedite vaccination, this project proposes to develop microneedle-based influenza vaccine patches that can be self-administered;do not produce sharp, biohazardous waste;and are low cost. Such patches could be rapidly distributed through pharmacies, fire stations or even the U.S. mail. Because microneedle patches target delivery to the skin's dendritic cells, lower vaccine doses should be needed, which is vital when vaccine supplies are limited. To accomplish these goals, this project has three Specific Aims.
Aim 1 will develop novel microneedle systems that are designed to deliver influenza vaccines to the skin. Microfabrication techniques will be developed to make microneedles that easily insert into skin to rapidly deliver vaccine to targeted depths. Microneedle designs will be compared in terms of their mechanical properties;stability during processing and storage;controlled dose targeting and kinetics of vaccine delivery.
Aim 2 will evaluate the efficacy of influenza vaccines delivered using microneedles to mice and hairless guinea pigs. Inactivated virus, detergent-split virus and purified HA protein will be compared as alternative vaccines, and selected adjuvants will be evaluated for their ability to enhance immune responses. The microneedle design and vaccination protocol will be optimized based on measuring humoral immune responses and protection against virus challenge. Secondary criteria will include cellular immune responses and memory B cell repertoire.
Aim 3 will determine the safety and stability of selected vaccine formulations, followed by GMP manufacturing of a pilot lot of the final product, and safety and toxicology studies of the final product. While the focus of the present application is on developing this system for prevention of seasonal influenza, the resulting information should also be applicable to novel vaccines for prevention of pandemic influenza.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI074579-04
Application #
7800863
Study Section
Special Emphasis Panel (ZAI1-CCH-M (M1))
Program Officer
Salomon, Rachelle
Project Start
2007-05-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$1,476,869
Indirect Cost
Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Le, Vy L; Courtney, Cynthia L; Steel, John et al. (2013) Closely related influenza viruses induce contrasting respiratory tract immunopathology. PLoS One 8:e76708
Koutsonanos, Dimitrios G; Compans, Richard W; Skountzou, Ioanna (2013) Targeting the skin for microneedle delivery of influenza vaccine. Adv Exp Med Biol 785:121-32
Choi, Hyo-Jick; Bondy, Brian J; Yoo, Dae-Goon et al. (2013) Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles. J Control Release 166:159-71
Koutsonanos, Dimitrios G; Vassilieva, Elena V; Stavropoulou, Anastasia et al. (2012) Delivery of subunit influenza vaccine to skin with microneedles improves immunogenicity and long-lived protection. Sci Rep 2:357
del Pilar Martin, Maria; Weldon, William C; Zarnitsyn, Vladimir G et al. (2012) Local response to microneedle-based influenza immunization in the skin. MBio 3:e00012-12
Weldon, William C; Zarnitsyn, Vladimir G; Esser, E Stein et al. (2012) Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine. PLoS One 7:e41501
Wrammert, Jens; Koutsonanos, Dimitrios; Li, Gui-Mei et al. (2011) Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208:181-93
Le, Thuc-vy L; Mironova, Elena; Garcin, Dominique et al. (2011) Induction of influenza-specific mucosal immunity by an attenuated recombinant Sendai virus. PLoS One 6:e18780
Weldon, William C; Martin, Maria P; Zarnitsyn, Vladimir et al. (2011) Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity. Clin Vaccine Immunol 18:647-54
Hossain, M Jaber; Bourgeois, Melissa; Quan, Fu-Shi et al. (2011) Virus-like particle vaccine containing hemagglutinin confers protection against 2009 H1N1 pandemic influenza. Clin Vaccine Immunol 18:2010-7

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