Nanocarriers of antigen proteins for vaccine delivery.

Nanoformulations in vaccinology provide antigen stability and enhanced immunogenicity, in addition to providing targeted delivery and controlled release. In the last years, much research has been focused on vaccine development using virus-like particles, liposomes, emulsions, polymeric, lipid, and inorganic nanoparticles. Importantly, nanoparticle interactions with innate and adaptive immune systems must be clearly understood to guide the rational development of nanovaccines. This review provides a recap and updates on different aspects advocating nanoparticles as promising antigen carriers and immune cell activators for vaccination. Moreover, it offers a discussion of how the physicochemical properties of nanoparticles are modified to target specific cells and improve vaccine efficacy.

Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis.

Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 µm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with Leishmania amazonensis, mice developed significantly lower parasite loads as compared with animals given naked LACK DNA or CCM alone. That was accompanied by increased stimulation of Th1-biased responses, as seen by the higher T-bet / GATA-3 ratio and IFN-γ levels. Together, these results demonstrate that CCM is a safe and effective mucopenetrating carrier that can increase the efficacy of i.n. LACK DNA vaccination against cutaneous leishmaniasis.

Vaccine Design against Chagas Disease Focused on the Use of Nucleic Acids.

Chagas disease is caused by the protozoan Trypanosoma cruzi and is endemic to Central and South America. However, it has spread around the world and affects several million people. Treatment with currently available drugs cause several side effects and require long treatment times to eliminate the parasite, however, this does not improve the chronic effects of the disease such as cardiomyopathy. A therapeutic vaccine for Chagas disease may be able to prevent the disease and improve the chronic effects such as cardiomyopathy. This vaccine would be beneficial for both infected people and those which are at risk in endemic and non-endemic areas. In this article, we will review the surface antigens of T. cruzi, in order to choose those that are most antigenic and least variable, to design effective vaccines against the etiological agent of Chagas disease. Also, we discuss aspects of the design of nucleic acid-based vaccines, which have been developed and proven to be effective against the SARS-CoV-2 virus. The role of co-adjuvants and delivery carriers is also discussed. We present an example of a chimeric trivalent vaccine, based on experimental work, which can be used to design a vaccine against Chagas disease.

Mesoporous Silicon Particles Favor the Induction of Long-Lived Humoral Responses in Mice to a Peptide-Based Vaccine.

Vaccinology faces the challenge of developing improved immunization approaches that are able to induce long-term immunity with the desired Th profile according to the pathology. In this context, new vehicles for efficient antigen delivery that exert adjuvant effects play a critical role in addressing this goal. Herein, mesoporous silicon particles (PSiP) were assessed as carriers for a peptide-based vaccine targeting the receptor for advanced glycation end products (RAGE), which is a relevant receptor in Alzheimer´s disease and other diseases. A RAGE peptide was adsorbed onto PSiP (PSiP vaccine) and administered to BALB/c mice, leading to immune responses that were similar in magnitude to those induced by the soluble peptide. However, the response induced by PSiP lasted for a significantly longer period when compared with the behavior of the group immunized with the peptide alone. Therefore, PSiP are proposed as carriers to enhance immune memory, which is critical in vaccination. This study opens interesting perspectives related to the application of PSiP in vaccinology.

Recombinant lactic acid bacteria as delivery vectors of heterologous antigens: the future of vaccination?

UNLABELLED: Lactic acid bacteria (LABs) are good candidates for the development of new oral vaccines and are attractive alternatives to attenuated pathogens. This review focuses on the use of wild-type and recombinant lactococci and lactobacilli with emphasis on their molecular design, immunomodulation and treatment of bacterial infections. The majority of studies related to recombinant LABs have focused on Lactococcus lactis, however, molecular tools have been successfully used for Lactobacillus spp. RESEARCH: Recombinant lactobacilli and lactococci have several health benefits, such as immunomodulation, restoration of the microbiota, synthesis of antimicrobial substances and inhibition of virulence factors. In addition, protective immune responses that are well tolerated are induced by the expression of heterologous antigens from recombinant probiotics.

Live bacterial vaccine vectors: An overview

Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.

Live bacterial vaccine vectors: An overview

Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.

Live bacterial vaccine vectors: an overview.

Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.