Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide&nbsp;microspheres could induce mice cytotoxic T-cell response

Abstract

Hepatitis C virus (HCV) is known to cause hepatitis and hepatocellular carcinoma. E2 envelope glycoprotein of HCV type (HCV-E2) has been reported to bind human host cells and is a major target for developing anti-HCV vaccines. However, the therapeutic vaccine for infected patients still needs further development. The vaccine aims to provide cytotoxic T-cells to eliminate infected cells and hepatocellular carcinoma. Currently, there is no effective HCV therapeutic vaccine because most chronically infected patients rarely generate cytotoxic T-cells, even though they have high levels of neutralizing antibodies. Therefore, the adjuvant must be applied to enhance the efficacy of the therapeutic vaccine. In this study, we constructed HCV1b-E2 recombinant protein, a truncated form of peptide, to combine with an effective vaccine adjuvant and delivery system by using poly d , l -lactic- co -glycolide (PLGA) microspheres. HCV1b-E2 protein was effectively encapsulated into PLGA microspheres (HCV1b-E2-PLGA) as a strategy to deliver an insoluble form of HCV1b-E2 protein. The size and shape of PLGA microspheres were generated properly to carry an insoluble form of viral peptide in vivo. The encapsulated viral protein was slowly and continuously released from PLGA microspheres, which indicated the property of the adjuvant. HCV1b-E2-PLGA can trigger a cell-mediated immune response by inducing an expression of mice CD8 + T-cells. Our results demonstrated that HCV1b-E2-PLGA-immunized mice have a significantly increased CD8 + T-cell number, whereas HCV1b-E2-immunized mice have a lower number of CD8 + T-cells. Moreover, HCV1b-E2-PLGA could induce a specific antibody to viral protein, and the immune cells could secrete IFN-γ, which is a significant cytokine for viral response. Thus, HCV1b-E2-PLGA is shown to have adjuvant property and efficacy in the murine model, which is a good strategy to develop HCV prophylactic and therapeutic vaccines.

PLGA Particles in Immunotherapy

“…In mice, immunized with the microparticulate vaccine, significantly higher CD8 + T cells responses against E2 compared to soluble immunizations were observed. Increased levels of ex vivo-secreted IFN-γ were measured upon PLGA particle immunization as well as a robust IgG antibody response [ 171 ].…”

Nanoparticle- and Microparticle-Based Vaccines against Orbiviruses of Veterinary Importance

“…Non-lipidic biodegradable nanocarrier- or microcarrier-based delivery platforms have been also assessed, mainly carbohydrate constructs and dendrimers. The most common polymeric nano- and microparticles are those based on poly(α-hydroxy acids) such as the Food and Drug Administration (FDA) and European Medicine Agency (EMA)-approved poly(lactic-coglycolic acid) (PLGA) or poly(lactic acid) (PLA)-based nanoparticles [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. In addition, poly-amino acids, such as poly(γ-glutamic acid) (γ-PGA) [ 40 ], poly(ε-lysine) [ 41 ] or poly(L-arginine) [ 42 ], and polysaccharides such as chitosan, alginate or dextran [ 43 , 44 , 45 , 46 , 47 ], have also been developed.…”

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

“…PLGA-NPs can also be used for the delivery of poor soluble proteins. Roopngam et al encapsulated the insoluble form of E2 envelope glycoprotein subtype 1b of hepatitis C virus (HCV1b-E2) in PLGA microspheres, showing that its continuous release from these microspheres induced a strong CD8 + T-cell immune response, as well as IFN-γ secretion in vaccinated mice [57]. Lastly, PLGA NPs have been used to deliver a multi-epitope vaccine against human T-cell leukemia/lymphoma virus type 1 (HTLV-1), an oncogenic RNA virus responsible for T-cell leukemia.…”