Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice

Abstract

There is no effective protective vaccine against human toxoplasmosis, which is a potential threat to nearly a third of the world population. Vaccines based on virus-like particles (VLPs) have been highly successful in humans for many years, but have rarely been applied against Toxoplasma gondii infection. In this study, we inserted a B cell epitope (SAG1 82−102 or SAG1 301−320 ), a CD8 + cell epitope (HF10 or ROP7), and a CD4 + cell epitope (AS15) of T. gondii into a truncated HBc Δ (amino acids1–149) particle to construct four chimeric VLP vaccine formulations, i.e., HBc ΔH82 , HBc ΔH301 , HBc Δ R82 , and HBc Δ R301 . When these chimeric HBc particles were expressed in Escherichia coli , they showed icosahedral morphology similar to that of the original VLPs and were evaluated as vaccine formulations against acute and chronic toxoplasmosis in a mouse model (BALB/c mice (H-2 d ). All these chimeric HBc VLPs induced strong humoral and cellular immune responses with high IgG antibody titers and interferon(IFN)-γ production. Only the mice immunized with HBc ΔH82 showed prolonged survival time (15.6 ± 3.8 vs. 5.6 ± 0.8 days) against acute infection with RH tachyzoites and decrease in brain parasite load (1,454 ± 239 vs. 2,091 ± 263) against chronic infection with Prugniuad cysts, as compared to the findings for the control group. These findings suggest that HBc VLPs would act as an effective carrier for delivering effective multiple antigenic epitopes and would be beneficial for developing a safe and long-acting vaccine against toxoplasmosis.

Parasite Infiltration and Apoptosis in Spleen upon Toxoplasma gondii Infection

“…As such, splenic infections were strictly limited to capsular areas of the spleen in 10 tachyzoites infected mice, while spleens of mice infected with higher doses were subjected to parasitic infiltration through the splenic capsule. Poor vaccine efficacies were observed from previous studies using high doses of tachyzoites for vaccine challenge experiment [5][6][7][8][9][10][11][12], indicating different vaccine efficacies might be concluded if low dosage of tachyzoites were used. Since all mice died from 10, 30, and 100 tachyzoites infections after spleen infiltration and apoptosis from 30 and 100 tachyzoites infected mice post-infection, we conclude that 30 tachyzoites dosage can be used for vaccine or apoptosis study.…”

“…Oocysts in the feces of definitive host can be ingested by other intermediate hosts, which results in infection. Mice as intermediate hosts are extensively used for pathogenesis and vaccine study of toxoplas-mosis, in which high numbers of tachyzoites of T. gondii (RH) (10 3 , 10 4 , 10 5 ) have been used [5][6][7][8][9][10][11][12]. T. gondii (RH) is highly virulent and its infection in mice causes death [13].…”

“…Mice infected with 10 5 tachyzoites show no CD8 + T and germinal center B cell responses from the spleen at day 16 post-infection, since these immune cells are largely damaged [12]. Low vaccine efficacies were reported upon challenge infection with T. gondii (RH) at high dosage (10 3 , 10 4 , 10 5 ), in which mice died at very early stage of infection and immune responses elicited by challenge infection cannot be detected [5][6][7][8][9][10][11]. Thus, finding correct infection dosage for challenge infection to evaluate vaccine efficacy and immune responses is extremely important.…”

In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection

“…An alternative strategy embraces the use of informatics to predict and assess MHC-II T-cell epitopes using criteria to maximize their in vivo protective potential. The fastgrowing application of VLP-based vaccines against several parasites, including Plasmodium spp [34,35], Leishmania infantum [36], Toxoplasma gondii [37], Trichinella spiralis [38], and Clonorchis sinensis [39] prompted our interest in developing a VLP-based vaccine against trichuriasis.…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…It is composed of three tandem repeat (R) and cell (T) epitopes from the circumsporozoite protein of the P. falciparum malaria parasite, which are displayed on hepatitis B surface particles (HBs-Ag) (S), co-expressed in Saccharomyces cerevisiae (S) and reconstituted with an AS01 adjuvant ( 115 ). The development of vaccines against Toxoplasma gondii ( 116 ), T . spiralis ( 117 ), Clonorchis sinensis vaccine ( 118 ), and T. trichiura ( 79 ) have all embraced VLP technology.…”