Alternative delivery of a thermostable inactivated polio vaccine

Abstract

In the near future oral polio vaccine (OPV) will be replaced by inactivated polio vaccine (IPV) as part of the eradication program of polio. For that reason, there is a need for substantial amount of safe and more affordable IPV for low-income countries. Bioneedles, which are biodegradable mini-implants, have the potential to deliver vaccines outside the cold-chain and administer them without the use of needles and syringes. In the current study, Bioneedles were filled with IPV, subsequently lyophilized, and antigenic recoveries were determined both directly after IPV-Bioneedle preparation as well as after elevated stability testing. Further, we assessed the immunogenicity of IPV-Bioneedles in rats and the residence time at the site of administration. Trivalent IPV was formulated in Bioneedles with recoveries of 101±10%, 113±18%, and 92±15%, respectively for serotypes 1, 2 and 3. IPV in Bioneedles is more resistant to elevated temperatures than liquid IPV: liquid IPV retained less than half of its antigenicity after 1 day at 45°C and IPV in Bioneedles showed remaining recoveries of 80±10%, 85±4% and 63±4% for the three serotypes. In vivo imaging revealed that IPV administered via Bioneedles as well as subcutaneously injected liquid IPV showed a retention time of 3 days at the site of administration. Finally, an immunogenicity study showed that IPV-filled Bioneedles are able to induce virus-neutralizing antibody titers similar to those obtained by liquid intramuscular injection when administered in a booster regime. The addition of LPS-derivate PagL in IPV-filled Bioneedles did not increase immunogenicity compared to IPV-Bioneedles without adjuvant. The current study demonstrates the pre-clinical proof of concept of IPV-filled Bioneedles as a syringe-free alternative delivery system. Further pre-clinical and clinical studies will be required to assess the feasibility whether IPV-Bioneedles show sufficient safety and efficacy, and may contribute to the efforts to eradicate and prevent polio in the future.

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses

“…While the lack of immune enhancement observed in the IPV3 responses is somewhat unexpected given the higher immune responses elicited with the Nanopatch for IPV1 and 2, there is precedent for this result. Previously, it has been reported that IPV3 produces relatively low responses compared to IPV1 and 2, when using fractional doses and/or solid IPV formulations 10 , 34 , 35 . This suggests the IPV3 component of the vaccine is possibly (1) less immunogenic than IPV1 and 2, or (2) not in excess.…”

Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

“…Another novel strategy for intradermal injection is microneedles, which are micron-sized needles (7). Microneedles were investigated on their ability to induce protective immune responses upon intradermal IPV delivery on rats and rhesus macaques (8)(9)(10)(11)(12). Hollow microneedle (HMN) mediated intradermal IPV immunization at reduced doses was also investigated in humans, which resulted in similar seroconversion rates in comparison to a full intramuscular dose (13).…”

Technologies to Improve Immunization

“…Administration of tetanus toxoid, hepatitis B, influenza, and IPVs via Bioneedles has been studied in animal models. [276][277][278][279] In Wistar rats, the same dose of IPV given by SC or IM liquid injection or by Bioneedle implantation was found to produce similar antibody titers after two immunizations.…”