Abstract
Toxoplasma gondii can infect almost all endotherm organisms including humans and cause life-threatening toxoplasmosis in immunocompromised individuals, which leads to serious public health problems. Developing an excellent vaccine against this disease is impending. In present study, we formulated a cocktail protein vaccine including the TgMIF, TgCDPK3, and Tg14-3-3 proteins, which play critical roles in T. gondii infection. The recombinant protein vaccines were constructed and assessed by vaccination in BALB/c mice. We organized the mice in various protein combination groups of vaccines, and all mice were immunized with corresponding proteins at 0, 2, and 4 weeks. The specific protective effects of the vaccines on mice against T. gondii were analyzed by the mensuration of cytokines, serum antibodies, splenocyte proliferation assay, survival time, and parasite cyst burden of mice after the challenge. The study indicated that mice immunized with all three multicomponent proteins vaccine triggered a strong immune response with highest levels of IFN-γ production and IgG antibody compared with the other two protein combinations and controls. Moreover, there was an increase in IL-4 production and antigen-specific lymphocyte proliferation. The parasite cysts were significantly reduced (resulting in an 82.7% reduction), and survival time was longer in immunized mice with three multicomponent proteins compared with the other groups of mice. The enhanced humoral and cell-mediated immunity indicated that the protein cocktail vaccine containing three antigens provided effective protection for mice. These results indicated that recombinant TgMIF, TgCDPK3, and Tg14-3-3 multicomponent proteins were potential candidates for vaccine against toxoplasmosis.
Highlights
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite
To evaluate whether immunization protocol (Supplementary Figure S2) with these three recombinant Toxoplasma proteins could elicit humoral responses, serum samples of six groups were collected on days 0, 14, and 28 postimmunization and 2 weeks after the final immunization, and IgG antibodies of mice in all groups were analyzed by enzyme-linked immunosorbent assay (ELISA)
Splenic lymphocytes of mice from G3 and G5 groups were slightly increased (p < 0.05); G6 mixed recombinant proteins significantly enhance proliferative response compared with PBS group (p < 0.001) (Figure 3A)
Summary
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. The life cycle of T. gondii is very complex and comprises two specific phases, sexual and asexual cycles. Toxoplasma gondii causes asymptomatic infections and continues to live in the host. Only one commercial vaccine is developed to control Toxoplasma-associated abortion in sheep, which comprises live tachyzoites of the S48 “incomplete” strain of T. gondii. Under the present scenario, developing an effective vaccine against toxoplasmosis is of vital importance [5]. Increasing evidence suggest that vaccination with simplex stage antigens only lead to partial protection [6]. It is, difficult to achieve a recombinant vaccine with complete protection against complex T. gondii infection with only one immunodominant antigen. The purpose of our study was to determine the protective efficacy of a multiprotein vaccine against acute or chronic T. gondii infection. TgMIF, TgCDPK3, and Tg14-3-3, which played important roles in T. gondii infection, were selected to be configured into a cocktail protein vaccine
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