Under many circumstances, prophylactic immunizations are considered as the only possible strategy to control infectious diseases. Considerable efforts are typically invested in immunogen selection but, erroneously, the route of administration is not usually a major concern despite the fact that it can strongly influence efficacy. The skin is now considered a key component of the lymphatic system with tremendous potential as a target for vaccination. The purpose of this review is to present the immunological basis of the skin-associated lymphoid tissue, so as to provide understanding of the skin vaccination strategies. Several strategies are currently being developed for the transcutaneous delivery of antigens. The classical, mechanical or chemical disruptions versus the newest approaches based on microneedles for antigen delivery through the skin are discussed herein.

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The immunology of pregnancy is an evolving consequence of multiple reciprocal interactions between the maternal and the fetal-placental systems. The immune response must warrant the pregnancy outcome (including tolerance to paternal antigens), but at the same time, efficiently respond to pathogenic challenges. Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. This review aims to give an overview of the current rationale on the maternal vaccination strategies for the protection of the newborn pig against ETEC. Newborn piglets are immunodeficient and naturally dependent on the maternal immunity transferred by colostrum for protection—a maternal immunity that can be obtained by vaccinating the sow during pregnancy. Our current knowledge of the interactions between the pathogen strategies, virulence factors, and the host immune system is aiding the better design of vaccination strategies in this particular and challenging host status. Challenges include the need for better induction of immunity at the mucosal level with the appropriate use of adjuvants, able to induce the most appropriate and long-lasting protective immune response. These include nanoparticle-based adjuvants for oral immunization. Experiences can be extrapolated to other species, including humans.

Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M ® skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99m TcO 4 − radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 µg antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA. Moreover, MNs were able to protect mice from an experimental infection with 1×10 6 CFU/mouse of S. flexneri four weeks after immunization. This work demonstrates for the first time the potential of outer membrane vesicle-loaded dissolving MNs for ID vaccination against enteropathogens like Shigella.Vaccines 2019, 7, 159 2 of 15 (SALT), formed by a great network of immune cells, including Langerhans cells (LC), lymphocytes, and dendritic cells (DCs), which recognize the antigens and present them in the proximal lymph nodes [3]. Different ID vaccination methods have been used already, such as the Mantoux technique, microinjection systems, or jet injectors, used for smallpox, rabies, or Bacillus Calmette-Guérin (BCG) vaccines. However, they require the use of needles [4]. Microneedle patches (MNs) have appeared as a novel and attractive approach for ID immunization [5]. They are painless devices formed by arrays of micron-size projections that can pass through the stratum corneum and epidermis without reaching the nerves of the dermis layer [6]. Thus, they are a self-administered, minimally invasive method, well tolerated by human patients in proof of concept trials [7,8], that can directly target the skin immune cells [9].Several types of MNs have been developed for the delivery of antigens: solid, coated, hollow, and dissolving MNs [10]. Among them, and based on their self-disabling properties, dissolving MNs (MNs) have been selected for this work. These MNs are made of a soluble matrix, generally a biocompatible polymer or polysaccharide, which includes the antigenic complex. After the array insertion into the skin, the needle tips dissolve and the antigenic cargo i...