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Nasal vaccination is a promising alternative to classical parental vaccination, as it is non-invasive and, in principle, capable of eliciting strong systemic and local immune responses. However, the protective efficacy of nasally administered antigens is often impaired because of delivery problems: free antigens are readily cleared from the nasal cavity, poorly absorbed by nasal epithelial cells and generally have low intrinsic immunogenicity. In this review paper, we describe the main physiological hurdles to nasal vaccine delivery, survey the progress made in technological approaches to overcome these hurdles and discuss emerging opportunities for improving nasal vaccines. According to current insights, encapsulation of the antigen into bioadhesive (nano)particles is a promising approach towards successful nasal vaccine delivery. These antigen-loaded particles can be tailor made by supplying them with targeting ligands, adjuvants or endosomal escape mediators to form the desired vaccine that provides long-lasting protective immunity. [ABSTRACT FROM AUTHOR]

Immunotherapies are changing the landscape of melanoma treatment, but 70% of the melanoma patients have no response to immune checkpoint inhibitors or oncolytic virus therapy. Thus, novel formulations are needed to improve the population benefiting from immunotherapy. Here, we report a combined therapeutic modality based on oncolytic virus nanovesicles composed of CaCl2, oncolytic virus Ad5, lecithin and cholesterol (Lipo-Cap–Ad5) with immune checkpoint blockade (anti-PD-1 antibody). We investigated in vivo antitumour activity, systemic toxicity and mechanism of antitumour immune responses of Lipo-Cap–Ad5 + anti-PD-1 blockade, in a murine B16F10 tumour xenograft model. Through a series of in vivo studies, we found that Lipo-Cap–Ad5 in combination with anti-PD-1 blockade drastically reduced the tumour growth by 76.6%, and prolonged animals' survival with no obvious toxicity observed in heart, liver and kidney. The combination therapy facilitates tumour infiltration of effector CD4+, CD8+ T cells and increases secretion of TNF-α and IFN-γ. Therefore, Lipo-Cap–Ad5 in combination with anti-PD-1 blockade can potentiate and activate the immune system synergistically, ultimately creating a pro-inflammatory environment. These results suggest that combination immunotherapy of Lipo-Cap–Ad5 and anti-PD-1 blockade developed in this study has promising applications to enhance therapeutic efficacy with the potential of being translated into clinical practice. [ABSTRACT FROM AUTHOR]

In this review, polymeric micelles as drug-targeting carriers are concisely explained. In the first introduction part, I describe a brief history of polymer micelle's research for drug targeting, and then I explain this review's focus. Since most other review articles concerning polymeric micelle carriers explain only what was achieved in the polymeric micelle's research, I describe this review by focusing on what was not done. In the second part, I take up three characteristics of polymeric micelle carriers by comparing their advantages and disadvantages, what was done and what was not done in the past studies, and what is easily achieved and what is difficult to be achieved with polymeric micelles. In the last part, I discuss three common problems of nano-sized drug carrier systems including polymeric micelles, and then I add a few comments on these problems. [ABSTRACT FROM AUTHOR]

Vaccination remains the most cost-effective method for preventing infectious diseases. Key to vaccine design is the development of immunological memory, which is an essential property of the adaptive immune system. Bacterial polysaccharide conjugate vaccines are the gold standard currently used to confer protection of the host by inducing humoral immune responses against T-cell-independent antigens. Conjugate vaccines are effective, but we propose that local mucosal immune responses are likely to also play an important role in inducing immunity, and they have been less explored than systemic and adaptive immune responses. Adjuvants have been used to improve the immune response to vaccine antigens, however, no mucosal adjuvant has been licensed for human use. Here we describe the recent progress in the use of mucosal adjuvants to achieve significant immune responses against T-cell-independent antigens. We also introduce the idea that studying the mechanisms that induce cell sub-populations with strong immunological memory may facilitate the design of novel vaccine formulations, in particular in cases of B-cell unresponsiveness to thymus-independent stimuli. [ABSTRACT FROM AUTHOR]

Similar to the low molecular weight traditional drugs, biopharmaceuticals are capable of producing not only therapeutic effects but also side effects provided if the dose of these compounds exceeds certain concentration and/or if the exposure duration of these compounds at subtoxic doses is being lengthened. In addition, a major drawback of biopharmaceuticals is the risk of antibody formation. Following the administration of biopharmaceuticals into human body, the formation of antidrug–antibody (ADA) or neutralizing antibody and other general immune system effects (including allergy, anaphylaxis, or serum sickness) are of clinical concern regarding therapeutic efficacy and patient safety. For example, drug-induced neutralizing antibodies to erythropoietin (EPO) result in pure red cell aplasia, whereas drug-induced acquired anti-factor VIII antibodies worsen the pathology associated with hemophilia. Since most of the already developed or under development biopharmaceuticals are to some extent immunogenic, the regulatory agencies insist to conduct potential ADA formation during the drug development process itself. This review encompasses a short overview on the clinical concerns of immunogenicity produced at cellular levels by growth hormone, interferon-α, EPO, factor VIII, and factor IX following their parenteral administration into human body. Clinical concerns related to immunogenicity produced by the biosimilar versions of these drugs are also presented wherever possible. [ABSTRACT FROM AUTHOR]

DNA vaccination is an attractive immunization method able to induce robust cellular immune responses in pre-clinical models. However, clinical DNA vaccination trials performed thus far have resulted in marginal responses. Consequently, strategies are currently under development to improve the efficacy of DNA vaccines. A promising strategy is the use of synthetic particle formulations as carrier systems for DNA vaccines. This review discusses commonly used synthetic carriers for DNA vaccination and provides an overview of in vivo studies that use this strategy. Future recommendations on particle characteristics, target cell types and evaluation models are suggested for the potential improvement of current and novel particle delivery systems. Finally, hurdles which need to be tackled for clinical evaluation of these systems are discussed. [ABSTRACT FROM AUTHOR]

The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation. [ABSTRACT FROM AUTHOR]