Search Results (5)

Nano-adjuvant vaccines could induce immune responses and enhance immunogenicity. However, the application and manufacturing of nano-adjuvant is hampered by its challenging scale-up, poor reproducibility, and low security. Therefore, the present study aimed to optimize the preparation nanoparticles (NPs) using FDA-approved biopolymer materials poly(lactic acid) (PLA) and cationic lipid didodecyl-dimethyl-ammonium bromide (DDAB), develop the scale-up process, and evaluate the stability and biosafety of it. The optimum preparation conditions of DDAB/PLA NPs on a small scale were as follows: DDAB amount of 30 mg, aqueous phase volume of 90 mL, stirring rate at 550 rpm, and solidifying time of 12 h. Under the optimum conditions, the size of the NPs was about 170 nm. In scale-up preparation experiments, the vacuum rotary evaporation of 6 h and the Tangential flow ultrafiltration (TFU) method were the optimum conditions. The results suggested that DDAB/PLA NPs exhibited a uniform particle size distribution, with an average size of 150.3 ± 10.4 nm and a narrow polydispersity index (PDI) of 0.090 ± 0.13, coupled with a high antigen loading capacity of 85.4 ± 4.0%. In addition, the DDAB/PLA NPs can be stored stably for 30 days and do not have side effects caused by residual solvents. For biosafety, the acute toxicity experiments showed good tolerance of the vaccine formulation even at a high adjuvant dose. The local irritation experiment demonstrated the reversibility of muscular irritation, and the repeated toxicity experiment revealed no significant necrosis or severe lesions in mice injected with the high-dose vaccine formulation. Overall, the DDAB/PLA NPs exhibit potential for clinical translation as a safe candidate vaccine adjuvant. Full article

Nanostructures have been of paramount importance for developing immunoadjuvants. They must be cationic and non-cytotoxic, easily assembling with usually oppositely charged antigens such as proteins, haptens or nucleic acids for use in vaccines. We obtained optimal hybrid nanoparticles (NPs) from the biocompatible polymer poly(methyl methacrylate) (PMMA) and the cationic lipid dioctadecyl dimethyl ammonium bromide (DODAB) by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB. NPs adsorbed ovalbumin (OVA) as a model antigen and we determined their adjuvant properties. Interestingly, they elicited high double immune responses of the cellular and humoral types overcoming the poor biocompatibility of DODAB-based adjuvants of the bilayer type. The results suggested that the novel adjuvant would be possibly of use in a variety of vaccines. Full article

Quaternary ammonium surfactants (QACs) are microbicides, whereas poly (acrylates) are biocompatible polymers. Here, the physical and antimicrobial properties of two QACs, cetyl trimethyl ammonium bromide (CTAB) or dioctadecyl dimethyl ammonium bromide (DODAB) in poly (methyl methacrylate) (PMMA) nanoparticles (NPs) are compared to those of QACs alone. Methyl methacrylate (MMA) polymerization using DODAB or CTAB as emulsifiers and initiator azobisisobutyronitrile (AIBN) yielded cationic, nanometric, homodisperse, and stable NPs. NPs’ physical and antimicrobial properties were assessed from dynamic light scattering (DLS), scanning electron microscopy, and viability curves of Escherichia coli, Staphylococcus aureus, or Candida albicans determined as log(colony-forming unities counting) over a range of [QACs]. NPs were spherical and homodisperse but activity for free QACs was higher than those for QACs in NPs. Inhibition halos against bacteria and yeast were observed only for free or incorporated CTAB in NPs because PMMA/CTAB NPs controlled the CTAB release. DODAB displayed fungicidal activity against C. albicans since DODAB bilayer disks could penetrate the outer glycoproteins fungus layer. The physical properties and stability of the cationic NPs highlighted their potential to combine with other bioactive molecules for further applications in drug and vaccine delivery. Full article

Hybrid and antimicrobial nanoparticles (NPs) of poly (methyl methacrylate) (PMMA) in the presence of poly (diallyl dimethyl ammonium) chloride (PDDA) were previously obtained by emulsion polymerization in absence of surfactant with low conversion. In the presence of amphiphiles such as cetyl trimethyl ammonium bromide (CTAB), dioctadecyl dimethyl ammonium bromide (DODAB) or soybean lecithin, we found that conversion increased substantially. In this work, the effect of the amphiphiles on the NPs core-shell structure and on the antimicrobial activity of the NPs was evaluated. NPs dispersions casted on silicon wafers, glass coverslips or polystyrene substrates were also used to obtain antimicrobial coatings. Methods for characterizing the dispersions and coatings were based on scanning electron microscopy, dynamic light scattering, determination of thickness, rugosity, and wettability for the coatings and determination of colony-forming unities (log CFU/mL) of microbia after 1 h interaction with the coatings or dispersions. The amphiphiles used during PMMA/PDDA/amphiphile NPs synthesis reduced the thickness of the NPs PDDA shell surrounding each particle. The antimicrobial activity of the dispersions and coatings were due to PDDA—the amphiphiles were either washed out by dialysis or remained in the PMMA polymeric core of the NPs. The most active NPs and coatings were those of PMMA/PDDA/CTAB—the corresponding coatings showed the highest rugosity and total surface area to interact with the microbes. The dispersions and coatings obtained by casting of the NPs dispersions onto silicon wafers were hydrophilic and exhibited microbicidal activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. In addition, a major effect of reduction in particle size revealed the suitability of nanometric and cationic NPs (sizes below 100 nm) represented by PMMA/PDDA/CTAB NPs to yield maximal microbicidal activity from films and dispersions against all microbia tested. The reduction of cell viability by coatings and dispersions amounted to 6–8 logs from [PDDA] ≥ minimal microbicidal concentration. Full article

After vaccination, vaccine components must activate the immune response, but the ideal vaccine should not result in undesirable effects in cattle. The aim of this study was to evaluate the inflammatory and humoral responses and adverse reactions induced by three adjuvanted commercial vaccines against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV-1). Holstein heifers (n = 35) were divided into four groups by adjuvant compounds: Vaccine A (Alum; n = 9), Vaccine B (Oil-in-water; n = 10), Vaccine C (Amphigen/Quil A cholesterol and dimethyl-dioctadecyl ammonium (DDA) bromide (QAD; n = 10), and Control (n = 6). Heifers were assessed at 0 h, 6, 24, 48, 72 and 168 h post-vaccination; serology was evaluated at first dose (D0), booster (D21) and D42. Heifers vaccinated with Vaccine B (p = 0.0001) and C (p = 0.0001) had a more intense local reaction, while there was a higher rectal temperature detected in heifers vaccinated with Vaccine C (p = 0.020). There was greater systemic reaction observed for heifers vaccinated with Vaccines B and C at 48 h (p = 0.002) after a second dose. Clinical pathology parameters [white blood count (WBC) (p = 0.001), neutrophils (p = 0.0001) and haptoglobin concentrations (p = 0.0001)] were higher in animals vaccinated with Vaccine C. Neutralizing Abs against BVDV type 1 strains, NADL and Singer, were detected in animals vaccinated with Vaccines A or C at D42, while BVDV-2 antibodies were detected only in animals vaccinated with Vaccine C. A BHV-1 antibody was detected in all three vaccine groups (Vaccines A, B or C) at day 42 (21 days post booster vaccination). The findings of this research were based on three different commercial laboratory formulations and also according to the conditions which the study was conducted. In this context, vaccine containing mineral oil or Amphigen/QAD presented greater local reactivity and induced a significant systemic inflammatory response. Vaccinated heifers with Alum and Amphigen/QAD commercial vaccines enhanced humoral immune response against BVDV and BHV-1. Full article