Immune response and reactogenicity of an unadjuvanted intradermally delivered human papillomavirus vaccine using a first generation Nanopatch™ in rhesus macaques: An exploratory, pre-clinical feasibility assessment
Brian K. Meyer,
Mark A.F. Kendall,
Donna M. Williams,
Andrew J. Bett,
Sheri Dubey,
Renee C. Gentzel,
Danilo Casimiro,
Angus Forster,
Holly Corbett,
Michael Crichton,
S. Ben Baker,
Robert K. Evans,
Akhilesh Bhambhani
Affiliations
Brian K. Meyer
New Technologies, Vaccine Drug Product Development, Vaccine Process Research and Development, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA; Corresponding author at: Merck & Co., Inc., 770 Sumneytown Pike, WP78-302, West Point, PA 19486, USA.
Mark A.F. Kendall
Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland QLD 4072, Australia; Vaxxas Pty Ltd, Translational Research Institute, 37 Kent Street, Brisbane, QLD 4102, Australia
Donna M. Williams
New Technologies, Vaccine Drug Product Development, Vaccine Process Research and Development, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Andrew J. Bett
Infectious Disease and Vaccines, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Sheri Dubey
Infectious Disease and Vaccines, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Renee C. Gentzel
Movement Disorders and Translation, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Danilo Casimiro
Infectious Disease and Vaccines, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Angus Forster
Vaxxas Pty Ltd, Translational Research Institute, 37 Kent Street, Brisbane, QLD 4102, Australia
Holly Corbett
Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland QLD 4072, Australia
Michael Crichton
Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland QLD 4072, Australia; Vaxxas Pty Ltd, Translational Research Institute, 37 Kent Street, Brisbane, QLD 4102, Australia
S. Ben Baker
Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland QLD 4072, Australia; Vaxxas Pty Ltd, Translational Research Institute, 37 Kent Street, Brisbane, QLD 4102, Australia
Robert K. Evans
New Technologies, Vaccine Drug Product Development, Vaccine Process Research and Development, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
Akhilesh Bhambhani
New Technologies, Vaccine Drug Product Development, Vaccine Process Research and Development, MRL, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
The human papillomavirus (HPV) 9-valent, recombinant vaccine (Gardasil™9) helps protect young adults (males and females) against anogenital cancers and genital warts caused by certain HPV genotypes (ref. Gardasil™9 insert). This vaccine is administered intramuscularly (IM). The aim of this study was to determine preclinically whether intradermal (ID) vaccination with an unadjuvanted 9-valent recombinant HPV vaccine using a first-generation ID delivery device, the Nanopatch™, could enhance vaccine immunogenicity compared with the traditional ID route (Mantoux technique). IM injection of HPV VLPs formulated with Merck & Co., Inc., Kenilworth, NJ, USA Alum Adjuvant (MAA) were included in the rhesus study for comparison. The Nanopatch™ prototype contains a high-density array comprised of 10,000 microprojections/cm2, each 250 µm long. It was hypothesized the higher density array with shallower ID delivery may be superior to the Mantoux technique. To test this hypothesis, HPV VLPs without adjuvant were coated on the Nanopatch™, stability of the Nanopatch™ with unadjuvanted HPV VLPs were evaluated under accelerated conditions, skin delivery was verified using radiolabelled VLPs or FluoSpheres®, and the immune response and skin site reaction with the Nanopatch™ was evaluated in rhesus macaques. The immune response induced by Nanopatch™ administration, measured as HPV-specific binding antibodies, was similar to that induced using the Mantoux technique. It was also observed that a lower dose of unadjuvanted HPV VLPs delivered with the first-generation Nanopatch™ and applicator or Mantoux technique resulted in an immune response that was significantly lower compared to a higher-dose of alum adjuvanted HPV VLPs delivered IM in rhesus macaques. The study also indicated unadjuvanted HPV VLPs could be delivered with the first-generation Nanopatch™ and applicator to the skin in 15 s with a transfer efficiency of approximately 20%. This study is the first demonstration of patch administration in non-human primates with a vaccine composed of HPV VLPs. Keywords: Vaccine, Vaccination, Nanopatch™, Microneedles, Patch, Intradermal, Rhesus, HPV, Virus-like particles, Skin, Micro array patch
