Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

David A Muller,Christiana Agyei-Yeboah,M Steven Oberste,Frances E Pearson,Paul R Young,Germain J.P Fernando,Jonathan C.J Wei,Simon R Corrie,Mark A F Kendall,Michael L Crichton,William C Weldon,Nick S Owens

doi:10.1038/srep22094

Abstract

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

Highlights

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016
This poses a challenge for mass vaccination campaigns since intramuscular inactivated polio vaccine (IPV) injections the need to be administered by trained health professionals
We began with establishing the coating formulation process for IPV2, to achieve a consistent coating across the Nanopatch surface and to maintain vaccine conformational stability throughout the coating/drying process

Summary

Introduction

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. Production costs for IPV have been estimated to be at least five times as much per dose as OPV primarily because of the additional manufacturing processes required for virus inactivation and the need for trained professional healthcare workers to deliver the vaccine intramuscularly (IM). At some point after polio has been eradicated and circulation of wild-type polioviruses has ceased, all OPVs will be withdrawn and IPV will be the only vaccine for poliomyelitis prevention This poses a challenge for mass vaccination campaigns (to control possible outbreaks of disease) since intramuscular IPV injections the need to be administered by trained health professionals. The combination of targeted vaccine together with inflammation resulting from localized cell death generated by the dynamic application of projections into the skin leads to improved immune responses over standard needle-based intradermal delivery (e.g. the Mantoux method)[11]

Methods

Results

Conclusion