A DNA vaccine against GII.4 human norovirus VP1 induces blocking antibody production and T cell responses.

Human noroviruses (HuNoVs) are highly contagious and a leading cause of epidemics of acute gastroenteritis worldwide. Among the various HuNoV genotypes, GII.4 is the most prevalent cause of outbreaks. However, no vaccines have been approved for HuNoVs to date. DNA vaccines are proposed to serve as an ideal platform against HuNoV since they can be easily produced and customized to express target proteins. In this study, we constructed a CMV/R vector expressing a major structural protein, VP1, of GII.4 HuNoV (CMV/R-GII.4 HuNoV VP1). Transfection of CMV/R-GII.4 HuNoV VP1 into human embryonic kidney 293T (HEK293T) cells resulted in successful expression of VP1 proteins in vitro. Intramuscular or intradermal immunization of mice with the CMV/R-GII.4 HuNoV VP1 construct elicited the production of blocking antibodies and activation of T cell responses against GII.4 HuNoV VP1. Our collective data support the utility of CMV/R-GII.4 HuNoV VP1 as a promising DNA vaccine candidate against GII.4 HuNoV.

Preparation of particle-attached microneedles using a dry coating process.

The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process. In this study, the authors introduce a novel microneedle system that involves physically attaching API particles to the biocompatible adhesive surface of the microneedles. To manufacture particle-attached microneedles, an adhesive surface was prepared by coating polydimethylsiloxane (PDMS) mixed with an elastomer base and a curing agent at a ratio of 40:1 (PDMS40) onto polylactic acid microneedles (PLA), and then attaching ovalbumin (OVA) particles with a mean diameter of 10 µm to the PDMS adhesive layer. The OVA particles were delivered for 5 min into porcine skin with a delivery efficiency of 93% ex vivo and into mouse skin with a delivery efficiency of over 90% in vivo. Finally, mouse experiments with OVA particle-attached microneedles showed a value of OVA antibody titer similar to that produced by intramuscular administration. Particle-attached microneedles are a novel microneedle system with a dry coating process and rapid API delivery into the skin. Particle-attached microneedles can provide a wide range of applications for administering drugs and vaccines.