Summary: The 19 kDa carboxy-terminal domain of Plasmodium yoelii merozoite surface protein-1 (MSP119) was expressed in Salmonella vaccine strains as a carboxy-terminal fusion to fragment C of tetanus toxin (TetC). This study demonstrates that antibodies that recognize disulphide-dependent conformational epitopes in native MSP1 react with the TetC-MSP119 fusion protein expressed in Salmonella. The proper folding of MSP119 polypeptide is dependent on both the Salmonella host strain and the protein to which the MSP119 polypeptide is fused. Serum from mice immunized with Salmonella typhimurium C5aroD expressing TetC-MSP119 recognized native MSP1 as shown by immunofluorescence with P. yoelii-infected erythrocytes. Antibody levels to MSP119 were highest in out-bred mice immunized with S. typhimurium C5aroD carrying pTECH2-MSP119 and antibody was mostly directed against reduction-sensitive conformational epitopes. However, antibody levels were lower than in BALB/c mice immunized with a glutathione S-transferase (GST)-MSP119 fusion protein in Freund's adjuvant, and which were protected against P. yoelii challenge infection. In challenge experiments with P. yoelii the Salmonella-immunized mice were not protected, probably reflecting the magnitude of the antibody response. The results of this study have important implications in the design of live multivalent bacterial vaccines against eukaryotic pathogens.
In immunotherapy with T cells genetically modified to express chimeric antigen receptors (CAR), autologous lymphocytes are extracted from the patient, genetically modified to obtain CAR-T cells, and reintroduced into the patient to attack cancer cells. The success of this therapy has been achieved in the area of CD19-positive leukemias and lymphomas, being approved for the treatment of non-Hodgkin's lymphomas, acute lymphoblastic leukemia, and multiple myeloma. CARs are proteins that combine antibody specificity with T-cell cytotoxicity. The most common toxicities associated with therapy were not predicted by preclinical testing and include cytokine release syndrome, neurotoxicity, and cytopenias. These toxicities are usually reversible. One of the main challenges facing the field is the high economic cost that therapy entails, so the search for ways to reduce this cost must be a priority. In addition, other challenges to overcome include the situation that not all patients are supplied with the product and the existence of long waiting times for the start of therapy. The aim of this review is to present the development of the structure of CAR-T cells, the therapies approved to date, the toxicity associated with them, and the advantages and limitations that they present as immunotherapy.
Chitosan (CS) and polyvinylpyrrolidone (PVP)-based nanoparticles (NPs) are promising carriers for drug delivery due to their biocompatibility, biodegradability, and intrinsic antimicrobial properties. This study explores CS-PVP NPs for the encapsulation and controlled release of synthetic compounds (bis-THTT, JH1, JH2) and natural antimicrobials (honey and propolis). NPs were synthesized via ionic gelation, optimizing CS:PVP and CS-PVP:sodium tripolyphosphate (TPP) ratios. The optimal formulation (CS:PVP 1:0.5) produced stable, homogeneous NPs. Characterization was performed using FTIR, TGA, XRD, and AFM. Encapsulation efficiencies ranged from 44–60%. Antimicrobial activity was evaluated against Escherichia coli and Staphylococcus aureus, showing significant inhibition for JH1-, JH2-, honey-, and propolis-loaded NPs against E. coli. Cytotoxicity assays on 3T3 fibroblasts confirmed the biocompatibility of all formulations at 5 and 10 µg/mL. In vitro release studies in artificial gastric fluid (pH 1.78) demonstrated sustained drug release over 180 min. These results confirm that CS-PVP NPs can effectively encapsulate and protect both synthetic and natural bioactive compounds, enhancing their therapeutic potential. The developed nanosystems represent a versatile and safe platform for antimicrobial drug delivery and may support future applications in biomedical therapies.
Propolis, known for its immunological and therapeutic properties due to flavonoids and phenolic acids, has been used in alternative medicine for many years. In Ecuador, the commercialization of stingless bee honey has been increasing recently, although the physical-chemical and biological characteristics of honey from each species are unknown due to their different behaviors and diets. The objective of this research was to synthesize chitosan nanoparticles by encapsulating commercial honey (NPMC), honey (NPMA), and propolis (NPP) from Tetragonisca angustula by ionic gelation and glutaraldehyde cross-linking. The polymeric nanoparticles were structurally characterized (TGA and FT-IR), and their antimicrobial activity against E. coli and S. aureus, cytotoxicity, and controlled release were evaluated in two phases at different pH levels, one gastric (pH 1.8) and intestinal (pH 7.4). FT-IR analysis of the polymeric nanoparticles revealed the presence of hydroxyl and alkyl groups. NPMA and NPP showed characteristic vibrations of flavonoids and C=O, regardless of the molecular weight of chitosan. In the TGA, the NPMC had decomposition efficiencies of 97.22% (LMW) and 92.10% (HMW). Propolis nanoparticles achieved encapsulation efficiencies of 94.31% and 89.21%. NPPA (HMW-chitosan-based nanoparticles encapsulating propolis from stingless bees) was the most effective against S. aureus. NPPB (LMW-chitosan-based nanoparticles encapsulating propolis from stingless bees) at 10 μg/mL showed higher cytotoxicity than NPMAA (HMW-chitosan-based nanoparticles encapsulating honey from stingless bees). In summary, propolis nanoparticles maintained efficiencies above 76%, while NPMC and NPMA exhibited loading capacities greater than 27%. In contrast, formulations with high molecular weight chitosan showed slightly lower values, although these differences were not statistically significant.