Investigating the weak antibody response to vaccination with inactivated polio virus serotype 3 when delivered by microneedle patch.

Eradication of poliomyelitis requires vaccination coverage approaching 100%, which means vaccinating children at locations with limited healthcare resources. Microneedle (MN) patches can simplify vaccination by enabling administration by personnel with limited training and reducing reliance on refrigerated distribution. Here, we report that IPV serotype 3 (IPV3) was much less immunogenic when administered by MN patch compared to intramuscular (IM) vaccination, generating a neutralizing antibody titer similar to a 90%-lower dose given IM. To study this effect further, we found that microneedle factors including MN patch manufacturing process and type of MN patches (dissolving versus coated); skin-related factors including skin-induced injury and unfavorable skin conditions; and IPV3-related factors including dilution media, aggregation state, and PEGylation could not explain the poor immunogenicity of IPV3. The only thing effective to increase the IPV3 immune response by MN patch was boosting with additional doses of IPV3, indicating that although a single dose of IPV3 by MN patch was not effective to generate neutralizing antibodies, it was effective to prime the immune system for an effective boosting response. While the MN patch remains an attractive option for IPV vaccination, especially in a multi-dose vaccination schedule, additional studies are needed to understand why a single dose of IPV3 generates weak neutralizing antibody responses when administered by MN patch.