Low Adenovirus Vaccine Doses Administered to Skin Using Microneedle Patches Induce Better Functional Antibody Immunogenicity as Compared to Systemic Injection

Abstract

Adenovirus-based vaccines are demonstrating promising clinical potential for multiple infectious diseases, including COVID-19. However, the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti-vector neutralizing immunity. Here we determined how dissolvable microneedle patches (DMN) for skin immunization can overcome this issue, using a clinically-relevant adenovirus-based Plasmodium falciparum malaria vaccine, AdHu5–PfRH5, in mice. Incorporation of vaccine into patches significantly enhanced its thermostability compared to the liquid form. Conventional high dose repeated immunization by the intramuscular (IM) route induced low antigen-specific IgG titres and high anti-vector immunity. A low priming dose of vaccine, by the IM route, but more so using DMN patches, induced the most efficacious immune responses, assessed by parasite growth inhibitory activity (GIA) assays. Administration of low dose AdHu5–PfRH5 using patches to the skin, boosted by high dose IM, induced the highest antigen-specific serum IgG response after boosting, the greatest skewing of the antibody response towards the antigen and away from the vector, and the highest efficacy. This study therefore demonstrates that repeated use of the same adenovirus vaccine can be highly immunogenic towards the transgene if a low dose is used to prime the response. It also provides a method of stabilizing adenovirus vaccine, in easy-to-administer dissolvable microneedle patches, permitting storage and distribution out of cold chain.

Microneedle arrays integrated with living organisms for smart biomedical applications

“…Their work also revealed the critical roles of different immune cells performed during the MNA vaccination ( Figure 2 A ) 49 . A similar immune response was observed when applying dissolving MNAs to deliver vaccines against malaria and HIV 50 , 53 , 54 .…”

Recent Advances in Polymer Microneedles for Drug Transdermal Delivery: Design Strategies and Applications

“…Flynn et al. [ 30 ] stored dissolving MNs loaded with AdHu5‐PfRH5 vaccine at 25 and 40 °C for up to 6 months. They found that the adenovirus vaccine incorporated into the patch was completely stable at 25 °C, and no vaccine degradation was observed at 40 °C for up to 2 months.…”

“…And the loaded drugs are released when the needles are dissolved or degraded in the body. [30,52] The detail characteristics of these four types of MNs are listed in Table 2.…”

“…In the MNs transdermal delivery strategy, the drugs are directly entered the human body through the capillaries, so it can eliminate the first-pass metabolism and prevent the deterioration of GIT. [29][30][31] Moreover, the needle will not touch the nerve endings and blood vessels, so it also can reduce the patient's pain and enhance the patient's compliance. [32][33][34][35][36][37] Compared with traditional transdermal delivery strategies, MNs technology can not only deliver high molecular weight drugs, but also increase the drug per- meability.…”

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems

“…Microneedle systems definitely have great potential to be used as means of immunization against pathogens that affect the mucosal tract. Given the broad advantages these delivery systems own, they are stable at room temperature [77,78,[88][89][90], easy to use, painless and comfortable [91] for the patient, and do not require trained personnel. All these features make them useful when considering mass immunization in a short period of time as required in times of pandemics.…”