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 Anthony Fernance 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, Ankilesh Bhambhani

Research output: Contribution to journalArticle

Abstract

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 15s 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.
Original languageEnglish
Article number100030
JournalVaccine: X
Volume2
Early online date20 Jun 2019
DOIs
Publication statusPublished - 9 Aug 2019

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Papillomavirus Vaccines
Papillomaviridae
Macaca mulatta
immune response
vaccines
skin (animal)
alum
Skin
Human papillomavirus 9
adjuvants
Condylomata Acuminata
Synthetic Vaccines
warts
recombinant vaccines
dosage
Primates
methodology
young adults
prototypes
Young Adult

Keywords

  • HPV
  • Intradermal
  • Micro array patch
  • Microneedles
  • Nanopatch™
  • Patch
  • Rhesus
  • Skin
  • Vaccination
  • Vaccine
  • Virus-like particles

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Meyer, Brian K. ; Kendall, Mark Anthony Fernance ; Williams, Donna M. ; Bett, Andrew J. ; Dubey, Sheri ; Gentzel, Renee C. ; Casimiro, Danilo ; Forster, Angus ; Corbett, Holly ; Crichton, Michael ; Baker, S. Ben ; Evans, Robert K. ; Bhambhani, Ankilesh. / 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. In: Vaccine: X. 2019 ; Vol. 2.
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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. / Meyer, Brian K.; Kendall, Mark Anthony Fernance; Williams, Donna M.; Bett, Andrew J.; Dubey, Sheri; Gentzel, Renee C.; Casimiro, Danilo; Forster, Angus; Corbett, Holly; Crichton, Michael; Baker, S. Ben; Evans, Robert K.; Bhambhani, Ankilesh.

In: Vaccine: X, Vol. 2, 100030, 09.08.2019.

Research output: Contribution to journalArticle

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AU - Meyer, Brian K.

AU - Kendall, Mark Anthony Fernance

AU - Williams, Donna M.

AU - Bett, Andrew J.

AU - Dubey, Sheri

AU - Gentzel, Renee C.

AU - Casimiro, Danilo

AU - Forster, Angus

AU - Corbett, Holly

AU - Crichton, Michael

AU - Baker, S. Ben

AU - Evans, Robert K.

AU - Bhambhani, Ankilesh

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N2 - 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 15s 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.

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KW - Microneedles

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KW - Patch

KW - Rhesus

KW - Skin

KW - Vaccination

KW - Vaccine

KW - Virus-like particles

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