Poly (D, L-lactide-co-glycolide) delivery system improve the protective efficacy of recombinant antigen TA4 against Eimeria tenella infection

Abstract

Eimeria tenella is a protozoan parasite endemic in chickens and is one of the causative agents of avian coccidiosis. The aim of this research was to determine if poly (D, L-lactide-co-glycolide) ( PLGA ) nanoparticles carrying recombinant TA4 protein of E. tenella ( rEtTA4 ) could improve the level of protective immunity against E. tenella challenge. Recombinant TA4 protein was expressed and purified. Poly (D, L-lactide-co-glycolide) loaded with rEtTA4 ( PLGA-rEtTA4 ) nanoparticles was prepared and was delivered to 2-week-old layer chickens via intramuscular inoculation. Chickens injected with PBS and PLGA nanoparticles were served as control groups. The rEtTA4 and PLGA-rEtTA4 nanoparticles induced changes of serum cytokines, IgY levels, and T lymphocytes subpopulation, and the protective efficacy against E. tenella challenge was evaluated. Results showed that both rEtTA4 and PLGA-rEtTA4 vaccination groups induced significantly higher levels of specific EtTA4 IgY antibody and IL-17 and higher proportion of CD8 + T lymphocytes. However, no significant differences were observed in the proportion of CD4 + T lymphocytes compared with the PBS control. Chickens immunized with rEtTA4 and PLGA-rEtTA4 prominently increased the BW gains and decreased oocyst output compared with chickens immunized with PBS and PLGA after oral challenge with E. tenella . Poly (D, L-lactide-co-glycolide) encapsulated rEtTA4 nanoparticles–immunized chickens significantly induced higher levels of interferon gamma, IL-6, and IL-17 and a little bit higher proportion of CD8 + T lymphocytes compared with rEtTA4 subunit vaccine–immunized chickens. Thus, PLGA encapsulated rEtTA4 nanoparticles appeared to have great potential to enhance the immune response and improved the protective efficacy against E. tenella infection. Our results provided available protective subunit vaccine rEtTA4 and PLGA loaded with rEtTA4 nanoparticles against coccidiosis and suggested that PLGA nanoparticles could be an effective adjuvant to enhance the protective efficacy of rEtTA4 subunit vaccine.

PLGA Nanospheres as Delivery Platforms for Eimeria mitis 1a Protein: A Novel Strategy to Improve Specific Immunity

“…The EE of PLGA-rEm14-3-3 nanospheres reached 89.35% ± 1.18%, while the EE of CS-rEm14-3-3 nanospheres was 83.46% ± 1.57% ( 56 ). With similar procedures, the EE of PLGA-rEtTA4 nanospheres reached 82.40% ± 0.06%, while the LC of PLGA-rEtTA4 nanospheres was 2.00% ± 0.01% ( 46 ). However, the EE of synthesized CS-PLGA-rOmp22 nanospheres in another paper was approximately 55%, while the LC was approximately 0.94% ( 57 ).…”

“…Nanotechnology-based vaccines offer the possibility to act as efficient and safe alternatives to traditional peptide-based subunit vaccines ( 51 , 52 ), and numerous techniques nowadays have been applied to formulate nanovaccines ( 46 , 53 ). Here, we encapsulated the rEm1a antigen in PLGA and CS nanospheres using double emulsion solvent evaporation and ionic gelation technique, respectively.…”

“…For vaccine studies against chicken coccidiosis, multiple vaccine adjuvants have been employed to induce prolonged and strengthened host immunity ( 89 ). Entrapped in PLGA nanospheres, recombinant E. tenella TA4 antigens showed enhanced immunoprotection against E. tenella infections ( 46 ). Immunization with recombinant E. acervulina emulsified in a novel adjuvant containing Carbopol, dimethyl dioctadecyl ammonium bromide, cholesterol, and Quil A could improve weight gains and inhibit outputs of fecal oocysts in E. acervulina -challenged birds ( 90 ).…”

“…The sera were subsequently separated and stored at -20°C. Based on the previous report ( 46 ), enzyme-linked immunosorbent assays (ELISAs) were conducted to investigate Em1a-specific serum antibody levels. Briefly, each well of the 96-well plates (Costar, Cambridge, MA, USA) was coated with 1 μg recombinant Em1a proteins (diluted to 10 μg/ml with carbonate-bicarbonate buffer pH 9.6) overnight at 4°C.…”

A multiepitope vaccine encoding four Eimeria epitopes with PLGA nanospheres: a novel vaccine candidate against coccidiosis in laying chickens

“…Surface antigens (SAGs) are critical in parasite attachment and invasion and are used as vaccine candidates [ 13 ]. Derived from SAGs, E. tenella SAG1 (also known as TA4 antigen) can induce cell-mediated immunity against E. tenella infections [ 14 ]. Based on the nucleotide homology of E. tenella SAG1, NA4 antigens from E. necatrix have also been identified and can induce a strong protective effect against E. necatrix [ 15 ].…”