Evaluating Efficacy and Safety of Intradermal Delivery of Vaccines through Microneedle(s) in Animals: Systematic Review Protocol (Preprint)

BACKGROUND Microneedles are defined as micron-sized projections that create microscopic holes to the skin on application so that drug molecules can penetrate across the outer layers of the skin into the dermis or deeper. Skin is a natural barrier for defense against invading pathogens. Additionally, the dermis possesses dendritic cells that are efficient for antigen presentation and initiating the cascade of immunogenic responses leading to antibody production. Therefore, intradermal delivery of vaccine antigens could be a safe and less invasive alternative for vaccine delivery compared with conventional intramuscular injection. OBJECTIVE We intend to undertake a systematic review of the literature to evaluate the efficacy and safety of intradermal delivery of vaccines using microneedles in animal models. METHODS In this systematic review, we will consider all study designs evaluating the safety and/or efficacy of intradermal delivery of vaccines using microneedles in animal models. Our search strategy will include free text terms and controlled vocabulary for, “microneedle”, “vaccine”, and “intradermal”. We will search literature through PubMed, Embase, Cochrane, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the SYRCLE’s tool particularly for controlled studies and OHAT Risk of Bias Rating Tool for case studies, case-control studies, non-randomized studies, and cohort studies, and CAMARADES checklist to appraise the quality of the included studies. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. The primary outcome to be measured is the efficacy of vaccine delivered through an intradermal route using microneedle(s) such as parameters of immunogenicity (for example antibody levels), sero-efficacy (for example sero-conversion), protective efficacy, etc. Secondary outcomes would include the safety of vaccines delivered through the intradermal route. This could include parameters to identify and/or quantify the timing and nature of local reactions, bleeding, systemic reactions, and death. Pain response during vaccination delivered through the intradermal route will also be evaluated. RESULTS This is a protocol for a systematic review; therefore, results are not available. CONCLUSIONS This is the first systematic review protocol aiming to assess the evidence on the efficacy and safety of intradermal delivery of vaccines using microneedles in various animal models. The findings will inform the safety and efficacy of intradermal delivery of vaccines in animal models, with the overall goal of considering the method for human vaccination as well. The results of this study will be published in a peer-reviewed journal. CLINICALTRIAL PROSPERO CRD42021236625