Hepatitis B surface antigen incorporated in dissolvable microneedle array patch is antigenic and thermostable

Abstract

Alternatives to syringe-based administration are considered for vaccines. Intradermal vaccination with dissolvable microneedle arrays (MNA) appears promising in this respect, as an easy-to-use and painless method. In this work, we have developed an MNA patch (MNAP) made of hydroxyethyl starch (HES) and chondroitin sulphate (CS). In swines, hepatitis B surface antigen (HBsAg) formulated with the saponin QS-21 as adjuvant, both incorporated in HES-based MNAP, demonstrated the same level of immunogenicity as a commercially available aluminum-adjuvanted HBsAg vaccine, after two immunizations 28 days apart. MNAP application was associated with transient skin reactions (erythema, lump, scab), particularly evident when the antigen was delivered with the adjuvant. The thermostability of the adjuvanted antigen when incorporated in the HES-based matrix was also assessed by storing MNAP at 37, 45 or 50 °C for up to 6 months. We could demonstrate that antigenicity was retained at 37 and 45 °C and only a 10% loss was observed after 6 months at 50 °C. Our results are supportive of MNAP as an attractive alternative to classical syringe-based vaccination.

Safety, tolerability, and immunogenicity of influenza vaccination with a high-density microarray patch: Results from a randomized, controlled phase I clinical trial

“…Microarray patches (MAPs) are being developed by a number of parties as an alternative method for vaccine delivery [1][2][3][4][5][6][7]. MAPs have several potential advantages compared with injection by needle and syringe (N&S), including improved thermostability, ease of use and a reduced need for skilled healthcare workers for administration, greater acceptability by healthcare workers and recipients, avoidance of needle-stick injuries, and avoidance of the need for reconstitution [8,9].…”

Hepatitis B vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques

“…Several studies in animal models have delivered the vaccine intradermally by jet injection, which yielded immune responses comparable to subcutaneous or IM injection . MNPs have also been used in animal studies to administer hepatitis B vaccines using microneedles as a pretreatment to permeabilize skin, followed by topical application of a vaccine‐containing solution, by coating metal microneedles with vaccine and by encapsulating vaccine in dissolving MNPs …”

“…18,22 MNPs have also been used in animal studies to administer hepatitis B vaccines using microneedles as a pretreatment to permeabilize skin, followed by topical application of a vaccine-containing solution, [23][24][25] by coating metal microneedles with vaccine 26 and by encapsulating vaccine in dissolving MNPs. 27,28 A critical aspect of MNP design is the use of materials and microneedle geometry that enable reliable insertion into skin without mechanical damage to the microneedles. Microneedle design also needs to account for skin deformation during microneedle insertion, which can be accomplished by using microneedles of sufficient length to account for deformation and maximal sharpness to minimize that deformation.…”

Recent advances of microneedles for biomedical applications: drug delivery and beyond

“… Microneedle type Material Vaccine (type) Key finding Ref. Dissolving microneedle Hydroxyethyl starch 70000 Hepatitis B surface antigen (protein) The antigenicity of the Hepatitis B adjuvant maintained for 6 months at 50 °C with only a 10% loss 101 Dissolving microneedle Hyaluronic acid Live attenuated BCG (bacteria) Vaccination using microneedle array mixed with Bacille Calmette–Guerin (BCG) powder did not provoked severe inflammation and bruise as compared to intradermal injection 102 Dissolving microneedle Sucrose Rabies vaccination (nucleic acid) A rabies DNA vaccine integrated with dissolving microneedle was ten-fold lower vaccine dose than full-dose intramuscular vaccination 103 Dissolving microneedle Poly-vinyl alcohol Influenza (virus) Microneedle patch was capable of improving vaccine immunogenicity and increasing vaccination coverage 104 Hollow microneedle Polyimide IgG and IgG1 (protein) Nanoparticulate vaccines were discovered for protein antigen to control immune response using hollow microneedle 99 Solid microneedle and hollow microneedle Silicone Ovalbumin (nucleic acid) Hollow microneedle patches delivered ovalbumin efficiently for in vivo immunization in contrast to solid microneedle patches 105 Coated microneedle Ceramic Diphtheria and tetanus toxoid (peptide) Ceramic nanoporous microneedle arrays have a better capability of transporting diphtheria toxoid and tetanus toxoid 100 …”