Zika Vaccine Microparticles (MPs)-Loaded Dissolving Microneedles (MNs) Elicit a Significant Immune Response in a Pre-Clinical Murine Model

Abstract

Although the global Zika epidemic in 2015–16 fueled vaccine development efforts, there is no approved Zika vaccine or treatment available to date. Current vaccine platforms in clinical trials are administered via either subcutaneous or intramuscular injections, which are painful and decrease compliance. Therefore, in the present study, we explored Zika vaccine microparticles (MPs)-loaded dissolving microneedles (MNs) with adjuvant MPs encapsulating Alhydrogel® and MPL-A® administered via the transdermal route as a pain-free vaccine strategy. We characterized the MNs for needle length, pore formation, and dissolvability when applied to murine skin. Further, we evaluated the in vivo efficacy of vaccine MPs-loaded MNs with or without adjuvants by measuring the immune response after transdermal immunization. The vaccine MPs-loaded dissolving MNs with adjuvants induced significant IgG, IgG1, and IgG2a titers in immunized mice compared to the untreated control group. After the dosing regimen, the animals were challenged with Zika virus, monitored for seven days, and sacrificed to collect spleen and lymph nodes. The lymphocytes and splenocytes from the immunized mice showed significant expressions of helper (CD4) and cytotoxic (CD8a) cell surface markers compared to the control group. Thus, this study puts forth a ‘proof-of-concept’ for a pain-free transdermal vaccine strategy against Zika.

Adjuvanted-SARS-CoV-2 Spike Protein-Based Microparticulate Vaccine Delivered by Dissolving Microneedles Induces Humoral, Mucosal, and Cellular Immune Responses in Mice

“…The study of MN delivery of vaccine antigen against SARS-CoV-2 has been in preclinical testing. However, this study reports the effects of the integration of microparticulate vaccine delivered via MN [ 14 , 40 , 47 ]. A phase 1 clinical trial was conducted for the “PittCoVacc” vaccine, which administered the spike protein suspension in an MN-based vaccine [ 48 , 49 ].…”

“…Microneedles were formulated using the spin-casting method previously established in our laboratory [ 14 , 15 , 47 , 62 , 64 ]. First, depending on the group, the corresponding RBD suspension, RBD MPs, and adjuvant MPs were added to the trehalose solution.…”

“…The percentage of antigen content in spike RBD MPs was measured using the Micro Bicinchoninic acid (BCA) assay according to the instructions from the manufacturer. The percentage of antigen content was measured as encapsulation efficiency using the following formula: Microneedles were formulated using the spin-casting method previously established in our laboratory [14,15,47,62,64]. First, depending on the group, the corresponding RBD suspension, RBD MPs, and adjuvant MPs were added to the trehalose solution.…”

Intranasal Immunization for Zika in a Pre-Clinical Model

“…In our study, we investigated our ZIKV MP vaccine with Alhydrogel ® (alum) and Monophosphoryl Lipid-A (MPL-A ® ) adjuvants in microparticulate form. Alhydrogel ® (alum) helps to stimulate a T-cell helper Th2 antibody-mediated response [ 21 ]. On the other hand, MPL-A ® helps to induce a Th1 T-cell helper response.…”

Dissolving Microneedles Loaded with Nanoparticle Formulation of Respiratory Syncytial Virus Fusion Protein Virus-like Particles (F-VLPs) Elicits Cellular and Humoral Immune Responses

“…There are several types of microneedles, such as solid microneedles and hollow microneedles; however, dissolving microneedles is one of the most sought-after methods of intradermal vaccination due to the fact of their versatility in loading different kinds of antigens [21]. Moreover, dissolving microneedles can also be loaded with different nanoparticles that will simply be released in the skin upon application [18,[22][23][24]. We have previously shown that when the F-VLP antigen is encapsulated into a PLGA polymeric nanoparticle matrix, it improves the immunogenicity in vitro [25].…”