Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.

The goal of this study is the preparation of safer coated microneedles so that tips remaining after the initial use are less likely to be reinserted on a second use. Twelve groups of uncoated microneedles (u-MNs) were prepared from the combination of three different aspect ratios (height to base width) and four kinds of polymer (polyethylene (PE), polypropylene (PP), nylon and polylactic acid (PLA)). After coating the u-MNs with polyvinyl alcohol formulation to make coated MNs (c-MNs), the force displacement of the u-MNs and the c-MNs was measured. The aspect ratio was reduced from 2.2, 2.5 and 3.0 with u-MNs to 1.3, 1.4 and 1.6 with c-MNs, respectively, after the coating formulation was applied to the MNs. All PLA MNs had a puncture performance of more than 95%. However, the puncture performance of u-MNs made of PE and of PP with a 3.0 aspect ratio was only 8% and 53%, respectively, whereas the rates of c-MNs made of PE and of PP were 82% and 95%, respectively. In animal experiments with PP MNs with a 3.0 aspect ratio, the 59% rate of puncture performance with u-MNs increased to above 96% with c-MNs and fell to 13% for r-MNs. Safe c-MNs can overcome the disadvantages of standard c-MNs by reducing the probable contamination of remaining tips after use. Safe c-MNs have advantages over standard c-MNs in terms of humidity resistance, reasonable cost, sterilization process and short processing time through the separate process of u-MN preparation and simple dip-coating.

Influenza vaccine-associated anaphylaxis is a very rare allergic reaction to vaccines, but the most concerning and life-threatening adverse reaction. Although the safety of influenza vaccines has been well documented, occasional cases of anaphylaxis in vaccinated patients have been reported. In this study, we analyzed the immunoglobulin E (IgE) response to whole influenza vaccines in a pediatric case of delayed-onset anaphylaxis after influenza vaccination. The patient showed elevated specific IgE levels against whole influenza vaccines, especially with split virion from egg-based manufacturing process. Specific IgE levels to influenza vaccines showed decreased over. We evaluated a causal relationship between influenza vaccine and anaphylaxis event by enzyme-linked immunosorbent assay. Delayed-onset anaphylaxis after influenza vaccination can occur in children without predisposing allergic diseases. In addition, the results suggested that formulation and production system of influenza vaccines could affect the probability of severe allergic reaction to vaccines.

Background and objectives: The development of a five-in-one vaccine microneedle patch (five-in-one MN patch) aims to address challenges in administering vaccines against Diphtheria (DT), Tetanus (TT), Pertussis (wP), Hepatitis B (HBsAg), and Haemophilus influenzae type b (Hib). Combining multiple vaccines into a single patch offers a novel solution to improve vaccine accessibility, stability, and delivery efficiency, particularly in resource-limited settings. Methods: The five-in-one MN patch consists of four distinct microneedle arrays: DT and TT vaccines are coated together on one array, while wP, HepB, and Hib vaccines are coated separately on individual arrays. The patch was tested for long-term stability (12 months at 25 °C) and evaluated for immunogenicity in mice and minipigs. Antibody titers were measured using ELISA to compare immune responses between microneedle-based delivery and traditional intramuscular (IM) injection. Results: The five-in-one MN patch demonstrated stable antigenicity for up to 12 months at room temperature. In animal studies, the patch induced antibody titers comparable to traditional IM injections for all vaccines. Notably, immunogenic responses to Pertussis and Haemophilus influenzae type b vaccines via microneedles were reported for the first time. The patch facilitated the simultaneous yet independent delivery of vaccines, preserving their immunogenicity without interference. Conclusions: The five-in-one MN patch represents a significant advancement in vaccine delivery by enabling stable, minimally invasive, and efficient immunization. Its innovative design addresses the critical limitations of combination vaccines and has the potential to enhance vaccine accessibility in low- and middle-income countries. Future studies will focus on optimizing patch application techniques and evaluating broader clinical applicability.

Shim DH, et al. Clin Exp Vaccine Res. 2019 Jan;8(1):70-76. https://doi.org/10.7774/cevr.2019.8.1.70