Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Recombinant Toxoplasma gondii MIF, CDPK3, and 14-3-3 Protein Cocktail Vaccine

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.

Comparison of the immune response and protection against the experimental Toxoplasma gondii infection elicited by immunization with the recombinant proteins BAG1, ROP8, and BAG1‐ROP8

“…29,30 IFN-γ is an irreplaceable cytokine, and as long as the infection is resolved, some of these cells survive in the body, forming an immune memory ready to fight T. gondii faster and more effectively on the second encounter; vaccination exploits this potential for adaptive immunity. 31 In this study, the IFN-γ levels for the recombinant proteins rTgBAG1, rTgROP8, and rTgBAG1-rTgROP8 were increased, and the rTgBAG1-rTgROP8 group produced the highest IFN-γ levels. Correspondingly, the rTgBAG1-TgROP8 group survived the infection with TgCtwh3 for the longest time (12 days).…”

“…Natural Killer (NK) cells are involved in innate immunity during acute toxoplasma infection and are essential for early protection through IFN‐γ, which upregulates antimicrobial effector mechanisms to control T. gondii , and IFN‐γ is crucial for the activation of a variety of antimicrobial activities that limit parasite replication 29,30 . IFN‐γ is an irreplaceable cytokine, and as long as the infection is resolved, some of these cells survive in the body, forming an immune memory ready to fight T. gondii faster and more effectively on the second encounter; vaccination exploits this potential for adaptive immunity 31 . In this study, the IFN‐γ levels for the recombinant proteins rTgBAG1, rTgROP8, and rTgBAG1‐rTgROP8 were increased, and the rTgBAG1‐rTgROP8 group produced the highest IFN‐γ levels.…”

Recent progress in vaccine development targeting pre-clinical human toxoplasmosis

“…Cocktail subunit vaccines conferred protection against types I and II T. gondii lineages. Intramuscular immunization with subunit proteins T. gondii macrophage migration inhibitory factor, calcium-dependent protein kinase 3, and the 14-3-3 protein resulted in complete protection against RH tachyzoite and PRU strains [ 31 ]. Given this circumstance, more research on improving these vaccines’ protective efficacy is required.…”

Toxoplasma WH3 Δrop18: A live attenuated vaccine against acute and chronic toxoplasmosis

“…Over the past decades, many efforts have been made to develop vaccines against toxoplasmosis. A large number of candidates including inactivated tachyzoites 20 , DNA vaccines 21 , recombinant proteins 22,23 , nanoparticle-based vaccines 24 , mixed cocktail vaccines 25 , and live attenuated parasites 26 have been studied in animal models and considerable progress has been obtained. Unfortunately, so far none of these candidates has been effective in blocking vertical transmission or eliminating tissue cysts 27,28 .…”