<p>Single-dose Ag85B-ESAT-6 loaded&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles confer protective immunity against tuberculosis</p>

Abstract

Background Bacillus Calmette–Guérin, the attenuated strain of Mycobacterium bovis , remains the only available vaccine against tuberculosis (TB). However, its ineffectiveness in adults against pulmonary TB and varied protective efficacy (0–80%) speak to an urgent need for the development of an improved and efficient TB vaccine. In this milieu, poly(lactic- co -glycolic acid) (PLGA), is a preferential candidate, due to such properties as biocompatibility, targeted delivery, sustained antigen release, and atoxic by-products. Methods In this study, we formulated PLGA nanoparticles (NPs) encapsulating the bivalent H1 antigen, a fusion of Mycobacterium tuberculosis (Mtb) Ag85B and ESAT6 proteins, and investigated its role in immunomodulation and protection against Mtb challenge. Using the classical water–oil–water solvent-evaporation method, H1-NPs were prepared, with encapsulation efficiency of 86.1%±3.2%. These spherical NPs were ~244.4±32.6 nm in diameter, with a negatively charged surface (ζ-potential −4±0.6 mV). Results Under physiological conditions, NPs degraded slowly and the encapsulated H1 antigen was released over a period of weeks. As a proof-of-concept vaccine candidate, H1 NPs were efficiently internalized by the THP-1 human macrophages. Six weeks after a single-dose vaccination, H1 NP–immunized C57BL/6J mice showed significant increase in the production of total serum IgG ( P <0.0001) and its isotypes compared to H1 alone, IgG 2a being the predominant one, followed by IgG 1 . Further, the cytokine-release profile of antigen-stimulated splenocyteculture supernatant indicated a strong T H 1-biased immunoresponse in H1 NP–vaccinated mice, with ~6.03- and ~2.8-fold increase in IFNγ and TNFα cytokine levels, and ~twofold and 1.6 fold increase in IL4 and IL10 cytokines, respectively, compared to H1 alone–immunized mice. In protection studies, H1 NP–vaccinated mice displayed significant reductions in lung and spleen bacillary load ( P <0.05) at 5-week post–Mtb H37Rv challenge and prolonged survival, with a mean survival time of 177 days, compared to H1 alone–vaccinated mice (mean survival time 80 days). Conclusion Altogether, our findings highlight the significance of the H1-PLGA nanoformulation in terms of providing long-term protection in mice with a single dose.

Applications of polymer-based nanoparticles in vaccine field

“…Studies have shown that PEG strengthens the PLA nanoparticles in gastrointestinal (GI) fluid stability and promotes the transmit of nanoparticles to the lymphatic system through the GI mucosa [86]. Mice immunized by PLGA nanoparticles encapsulating the bivalent H1 antigen showed significant effects against tuberculosis, as the immunization provides longterm protection [87]. The limitations of PLGA nanoparticles can be overcome through extensive and comprehensive assessments of pharmacokinetics, biodistribution, and toxicity [27].…”

<p>The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant</p>

“…Th2-type cytokines (IL-4, IL-6) play important roles in humoral response. [50][51][52][53] In Figure 8, CYPP-PEI/PCV-2 significantly promoted the levels of IFN-r, TNF-a (Th1-type cytokines), IL-4, and IL-6 (Th2-type cytokines), which indicated that CYPP-PEI nanoparticles could promote both Th1-type and Th2-type immune response. Although the content of Th2-type cytokines (IL-4, IL-6) in the CYPP-PEI group increased obviously compared with PCV-2, CYP/ PCV-2, BP/PCV-2, and control groups, their expression levels were significantly lower than Th1-type cytokines.…”

<p>Ethosomal Gel for Improving Transdermal Delivery of Thymosin β-4</p>

“…The nanoparticle size, size distribution and zeta potentials of diluted Tβ-4 ethosome solution were measured using the Malvern Zetasizer Nano ZS system (Malvern, Westborough, UK) 15. The microstructure of Tβ-4 ethosomes was detected using a TEM (JEM 1200EX, JEOL, Tokyo, Japan) by dropping Tβ-4 ethosome solution onto special carbon-coated copper grids and dyeing with phosphotungstic acid (2%, w/w) for 10–15 s.…”