Search Results (23)

Anthralin has a long history as a topical treatment for psoriasis, where it reduces keratinocyte hyper-proliferation and effectively clears plaques. While it lowers inflammatory markers in psoriatic skin, it paradoxically induces inflammation in healthy skin through reactive oxygen species (ROS) and related pathways. However, its precise mechanism of action remains incompletely understood. Interestingly, the once undesirable pro-inflammatory effect in healthy skin may now represent a valuable adjuvant property for transcutaneous immunization (TCI). In particular, combining anthralin with the TLR7 agonist imiquimod (IMQ) elicits strong cytotoxic T-cell responses in pre-clinical studies. When paired with antigenic peptides that can penetrate the skin, this immunization approach is especially promising in the context of cancer therapy, given the central role of cytotoxic T-cells in tumor rejection. However, current evidence is largely derived from mouse models, but its efficacy and safety in humans remain to be established. This review therefore examines whether anthralin can be repurposed as a cutaneous adjuvant for transcutaneous immunization, and which mechanistic and translational constraints must be overcome before human application. Full article

Simple and non-invasive transdermal vaccination is an attractive alternative to conventional injection-based immunization. However, the effectiveness of transdermal vaccines is often constrained by the stratum corneum barrier. Although the use of solid-in-oil (S/O) nanodispersion technology has successfully facilitated skin permeation to induce an immunological response, the antibody titers remain suboptimal. Herein, a dectin-1 selective ligand, laminarin, was used as an immunostimulatory adjuvant to enhance the immune response. S/O nanodispersions loaded with laminarin and ovalbumin (OVA) were systematically developed and characterized in terms of particle size, in vitro OVA release behavior, and skin permeation performance using excised mouse skin. In vivo immunization via transcutaneous administration was performed to evaluate biocompatibility and antigen-specific immunoglobulin-G (IgG) responses. Laminarin-loaded S/O nanodispersions demonstrated long-term stability and efficient ex vivo skin permeability. All the prepared laminarin-loaded S/O nanodispersions showed increased OVA-specific IgG responses compared with the laminarin-free S/O formulation. Among the formulations, the S/O nanodispersion containing OVA and laminarin at a 1:4 weight ratio induced 20-fold higher OVA-specific IgG responses than PBS and 7-fold higher responses than laminarin-free S/O formulations. This study clearly demonstrates the potential of laminarin-loaded S/O nanodispersions as a non-invasive vaccine delivery platform for enhancing antigen-specific antibody responses. Full article

Recent advances in biotechnology have fundamentally reshaped the landscape of vaccine development, offering innovative strategies to improve immunogenicity, safety and accessibility. This review explores the cutting-edge platforms—including mRNA, DNA, virus-like particles, viral and bacterial vectors, and bacteriophage-based vaccines—that are redefining how vaccine antigens are delivered to the immune system. We also discuss alternative delivery methods, such as transcutaneous and mucosal immunization, which have the potential to improve vaccine acceptance and distribution, as well as next-generation adjuvants targeting innate immune receptors aiming to further enhance vaccine efficacy, especially in vulnerable populations. By synthesizing these innovations, this review highlights how biotechnology is enabling the design of safer, more efficient, and more adaptable vaccines to address both existing and emerging infectious diseases. Full article

Vaccination represents a critical preventive strategy in the current global healthcare system, serving as an indispensable intervention against diverse pathogenic threats. Although conventional immunization relies predominantly on hypodermic needle-based administration, this method carries substantial limitations, including needle-associated fear, bloodborne pathogen transmission risks, occupational injuries among healthcare workers, waste management issues, and dependence on trained medical personnel. Microneedle technology has emerged as an innovative vaccine delivery system, offering convenient, effective, and minimally invasive administration. These microscale needle devices facilitate targeted antigen delivery to epidermal and dermal tissues, where abundant populations of antigen-presenting cells, specifically Langerhans and dermal dendritic cells, provide robust immunological responses. Multiple research groups have extensively investigated microneedle-based vaccination strategies. This transdermal delivery technique offers several advantages, notably circumventing cold-chain requirements and enabling self-administration. Numerous preclinical investigations and clinical trials have demonstrated the safety profile, immunogenicity, and patient acceptance of microneedle-mediated vaccine delivery across diverse immunization applications. This comprehensive review examines the fundamental aspects of microneedle-based immunization, including vaccination principles, transcutaneous immunization strategies, and microneedle-based transdermal delivery—including classifications, advantages, and barriers. Furthermore, this review addresses critical technical considerations, such as treatment efficacy, application methodologies, wear duration, dimensional optimization, manufacturing processes, regulatory frameworks, and sustainability considerations, followed by an analysis of the future perspective of this technology. Full article

Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model. Full article

Given the limitations of conventional invasive vaccines, such as the requirement for a cold chain system and trained personnel, needle-based injuries, and limited immunogenicity, non-invasive vaccines have gained significant attention. Although numerous approaches for formulating and administrating non-invasive vaccines have emerged, each of them faces its own challenges associated with vaccine bioavailability, toxicity, and other issues. To overcome such limitations, researchers have created novel supplementary materials and delivery systems. The goal of this review article is to provide vaccine formulation researchers with the most up-to-date information on vaccine formulation and the immunological mechanisms available, to identify the technical challenges associated with the commercialization of non-invasive vaccines, and to guide future research and development efforts. Full article

Transcutaneous vaccination is one of the successful, affordable, and patient-friendly advanced immunization approaches because of the presence of multiple immune-responsive cell types in the skin. However, in the absence of a preferable facilitator, the skin’s outer layer is a strong impediment to delivering biologically active foreign particles. Lipid-based biocompatible ionic-liquid-mediated nanodrug carriers represent an expedient and distinct strategy to permit transdermal drug delivery; with acceptable surfactants, the performance of drug formulations might be further enhanced. For this purpose, we formulated a lipid-based nanovaccine using a conventional (cationic/anionic/nonionic) surfactant loaded with an antigenic protein and immunomodulator in its core to promote drug delivery by penetrating the skin and boosting drug delivery and immunogenic cell activity. In a follow-up investigation, a freeze–dry emulsification process was used to prepare the nanovaccine, and its transdermal delivery, pharmacokinetic parameters, and ability to activate autoimmune cells in the tumor microenvironment were studied in a tumor-budding C57BL/6N mouse model. These analyses were performed using ELISA, nuclei and HE staining, flow cytometry, and other biological techniques. The immunomodulator-containing nanovaccine significantly (p < 0.001) increased transdermal drug delivery and anticancer immune responses (IgG, IgG1, IgG2, CD8+, CD207+, and CD103+ expression) without causing cellular or biological toxicity. Using a nanovaccination approach, it is possible to create a more targeted and efficient delivery system for cancer antigens, thereby stimulating a stronger immune response compared with conventional aqueous formulations. This might lead to more effective therapeutic and preventative outcomes for patients with cancer. Full article

The advantages of skin-based vaccination include induction of strong immunity, dose-sparing, and ease of administration. Several technologies for skin-based immunisation in humans are being developed to maximise these key advantages. This route is more conventionally used in veterinary medicine. Skin-based vaccination of pigs is of high relevance due to their anatomical, physiological, and immunological similarities to humans, as well as being a source of zoonotic diseases and their livestock value. We conducted a systematic mapping review, focusing on vaccine-induced immunity and safety after the skin immunisation of pigs. Veterinary vaccines, specifically anti-viral vaccines, predominated in the literature. The safe and potent skin administration to pigs of adjuvanted vaccines, particularly emulsions, are frequently documented. Multiple methods of skin immunisation exist; however, there is a lack of consistent terminology and accurate descriptions of the route and device. Antibody responses, compared to other immune correlates, are most frequently reported. There is a lack of research on the underlying mechanisms of action and breadth of responses. Nevertheless, encouraging results, both in safety and immunogenicity, were observed after skin vaccination that were often comparable to or superior the intramuscular route. Further research in this area will underlie the development of enhanced skin vaccine strategies for pigs, other animals and humans. Full article

Breast milk is crucial in the development of late-onset breast milk jaundice (BMJ), possibly due to the composition of breast milk and the lactating mother’s diet. To explore the possible nutritional pathogenesis of late-onset BMJ, we investigated the lactation diet and collected breast milk by following the 42-day postpartum mother–infants pairs in Beijing and a total of 94 pairs were enrolled. The macronutrient content of breast milk was measured, and the epidermal growth factor (EGF) content in breast milk was determined by ELISA. Data on in-hospital and out-of-hospital breastfeeding, infant growth, jaundice-related vaccination, and puerperium diet were collected. The BMJ group received the second dose of hepatitis B vaccine later than the control group, and the difference was statistically significant (p < 0.001). The EGF concentration in breast milk was lower in the BMJ group than in the control group (p = 0.03). When EGF increased by 1 ng/mL, the transcutaneous bilirubin (TcB) value decreased by 0.33 ng/mL and 0.27 ng/mL before and after the adjustment, respectively. A 1 g increase in oil intake led to a 0.38 ng/mL increase in EGF concentration before the adjustment. With a 1 g increase in oil intake, the TcB value decreased by 0.27 ng/mL before the adjustment, and with a 1 g increase in soybean and soybean product intake, the TcB value decreased by 0.34 ng/mL after the adjustment. Collectively, EGF in breast milk may inhibit the occurrence of late-onset BMJ, and the dietary intake of oil in lactating mothers may affect the level of EGF in breast milk, thus affecting the occurrence of late-onset BMJ. Finally, dietary oil intake may be a protective factor for the occurrence of late-onset BMJ by increasing EGF levels in breast milk. Full article

Smallpox is an acute contagious disease caused by the variola virus. According to WHO guidelines, the smallpox vaccine is administrated by scarification into the epidermis using a bifurcated needle moistened with a vaccine solution. However, this invasive vaccination method involving multiple skin punctures requires a special technique to inoculate, as well as a cold chain for storage and distribution of vaccine solutions containing a live virus. Here, we report a transcutaneous smallpox vaccination using a live vaccinia-coated microneedle (MN) patch prepared by a low-temperature multiple nanoliter-level dispensing system, enabling accurate transdermal delivery of live vaccines and maintenance of bioactivity. The live vaccinia in hyaluronic acid (HA) solutions was selectively coated on the solid MN tips, and the coating amount of the vaccine was precisely controlled through a programmed multiple dispensing process with high accuracy under low temperature conditions (2–8 °C) for smallpox vaccination. Inoculation of mice (BALB/C mouse) with the MN patch coated with the second-generation smallpox vaccine increased the neutralizing antibody titer and T cell immune response. Interestingly, the live vaccine-coated MN patch maintained viral titers at −20 °C for 4 weeks and elevated temperature (37 °C) for 1 week, highlighting improved storage stability of the live virus formulated into coated MN patches. This coated MN platform using contact dispensing technique provides a simple and effective method for smallpox vaccination. Full article

In this study, we investigated the mechanism of transcutaneous adjuvant activity of the CpG-oligonucleotide (K3) in mice. Transcutaneous immunization (TCI) with an ovalbumin-loaded self-dissolving microneedle patch (OVA-sdMN) and K3-loaded hydrophilic gel patch (HG) increased OVA-specific Th2- and Th1-type IgG subclass antibody titers more rapidly and strongly than those after only OVA-sdMN administration. However, the antigen-specific proliferation of OVA-specific CD4⁺ T cells was similar between the OVA-only and the OVA+K3 groups. Population analysis of various immune cells in draining lymph nodes (dLNs) in the primary immune response revealed that the OVA+K3 combination doubled the number of dLN cells, with the most significant increase in B cells. Phenotypic analysis by flow cytometry revealed that B-cell activation and maturation were promoted in the OVA+K3 group, suggesting that direct B-cell activation by K3 largely contributed to the rapid increase in antigen-specific antibody titer in TCI. In the secondary immune response, a significant increase in effector T cells and effector memory T cells, and an increase in memory B cells were observed in the OVA+K3 group compared with that in the OVA-only group. Thus, K3, as a transcutaneous adjuvant, can promote the memory differentiation of T and B cells. Full article

Most viruses use several entry sites and modes of transmission to infect their host (parenteral, sexual, respiratory, oro-fecal, transplacental, transcutaneous, etc.). Some of them are known to be essentially transmitted via arthropod bites (mosquitoes, ticks, phlebotomes, sandflies, etc.), and are thus named arthropod-borne viruses, or arboviruses. During the last decades, several arboviruses have emerged or re-emerged in different countries in the form of notable outbreaks, resulting in a growing interest from scientific and medical communities as well as an increase in epidemiological studies. These studies have highlighted the existence of other modes of transmission. Among them, mother-to-child transmission (MTCT) during breastfeeding was highlighted for the vaccine strain of yellow fever virus (YFV) and Zika virus (ZIKV), and suggested for other arboviruses such as Chikungunya virus (CHIKV), dengue virus (DENV), and West Nile virus (WNV). In this review, we summarize all epidemiological and clinical clues that suggest the existence of breastfeeding as a neglected route for MTCT of arboviruses and we decipher some of the mechanisms that chronologically occur during MTCT via breastfeeding by focusing on ZIKV transmission process. Full article

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (PfMSP-Fu₂₄) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu₂₄ conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu₂₄ upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu₂₄-laden elastic liposomes (EL-PfMSP-Fu₂₄) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-Fu₂₄ and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-PfMSP-Fu₂₄ through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-Fu₂₄ was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against PfMSP-Fu₂₄ and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response. Full article

In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic. This review will provide an overview of the diverse range of vaccination techniques available to target the dermal compartment, as well as their current state, challenges, and prospects, and touch upon the formulations that have been developed to maximally benefit from these new techniques. These include needle and syringe techniques, microneedles, DNA tattooing, jet and ballistic delivery, and skin permeabilization techniques, including thermal ablation, chemical enhancers, ablation, electroporation, iontophoresis, and sonophoresis. Full article

In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications. Full article