Dissolvable microneedle patches for the delivery of cell-culture-derived influenza vaccine antigens.

Microneedle patches are gaining increasing attention as an alternative approach for the delivery of vaccines. In this study, a licensed seasonal influenza vaccine from 2007 to 2008 was fabricated into dissolvable microneedles using TheraJect's microneedle technology (VaxMat). The tips of the microneedles were made of antigens mixed with trehalose and sodium carboxymethyl cellulose. The patches containing 15 μg per strain of the influenza antigen were characterized extensively to confirm the stability of the antigen following fabrication into microneedles. The presence of excipients and very low concentrations of the vaccine on the microneedle patches made it challenging to characterize using the conventional single radial immunodiffusion analysis. Novel techniques such as capture enzyme-linked immunosorbent assay and enzyme digestion followed by mass spectroscopy were used to characterize the antigens on the microneedle patches. The in vivo studies in mice upon microneedle administration show immunogenicity against monovalent H1N1 at doses 0.1 and 1 μg and trivalent vaccine at a dose of 1 μg. The initial data from the mouse studies is promising and indicates the potential use of microneedle technology for the delivery of influenza vaccine.

[1]  M. Prausnitz,et al.  Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge , 2009, Proceedings of the National Academy of Sciences.

[2]  Göran Stemme,et al.  Painless Drug Delivery Through Microneedle-Based Transdermal Patches Featuring Active Infusion , 2008, IEEE Transactions on Biomedical Engineering.

[3]  M. Kendall,et al.  Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays. , 2010, Small.

[4]  J. Gregersen.  A quantitative risk assessment of exposure to adventitious agents in a cell culture-derived subunit influenza vaccine , 2008, Vaccine.

[5]  R. Albrecht,et al.  Innate immune evasion strategies of influenza viruses. , 2010, Future microbiology.

[6]  R. Bugarini,et al.  Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: a sequential Phase I and Phase II clinical trial. , 2009, Vaccine.

[7]  Mark R Prausnitz,et al.  Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Harry Greenberg,et al.  Novel generations of influenza vaccines. , 2003, Vaccine.

[9]  Michel Cormier,et al.  Microneedle-based vaccines. , 2009, Current topics in microbiology and immunology.

[10]  Robert Langer,et al.  Transdermal drug delivery , 2008, Nature Biotechnology.

[11]  J. Stockman,et al.  Dissolving polymer microneedle patches for influenza vaccination , 2012 .

[12]  R. Rappuoli,et al.  Novel Approaches to Vaccine Delivery , 2004, Pharmaceutical Research.

[13]  P. van Damme,et al.  Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. , 2009, Vaccine.

[14]  V. Nguyen,et al.  Perception and acceptance of intradermal influenza vaccination: Patient reported outcomes from phase 3 clinical trials , 2010, Human vaccines.

[15]  S. Halperin,et al.  Trivalent MDCK cell culture-derived influenza vaccine Optaflu® (Novartis Vaccines) , 2009, Expert review of vaccines.

[16]  P. Laurent,et al.  Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system. , 2007, Vaccine.