Abstract
Toxoplasmosis may pose a serious threat for individuals with weakened or undeveloped immune systems. However, to date, there is no specific immunoprophylaxis for humans. Thus, the aim of this study was to evaluate the immunogenicity of three trivalent—SAG2-GRA1-ROP1L (SGR), SAG1L-MIC1-MAG1 (SMM), and GRA1-GRA2-GRA6 (GGG)—and two tetravalent—SAG2-GRA1-ROP1-GRA2 (SGRG) and SAG1-MIC1-MAG1-GRA2 (SMMG)—chimeric T. gondii proteins, as well as their protective potential against chronic toxoplasmosis in laboratory mice. All three trivalent recombinant proteins possessed immunogenic properties, as defined by specific humoral and cellular responses in vaccinated mice characterized by the synthesis of specific IgG (IgG1/IgG2a) antibodies in vivo and the release of Th1/Th2 cytokines by stimulated splenocytes in vitro. Immunization with all three recombinant proteins provided partial protection against toxoplasmosis, although the protective capacity strongly depended on the individual antigenic composition of each preparation. The antigens providing the highest (86%) and lowest (45%) protection, SGR and SMM, respectively, were supplemented with GRA2 antigen fragment, to form the tetravalent chimeric proteins SGRG and SMMG. Further study revealed that the tetravalent preparations exhibited high immunogenic potential; however, the addition of another antigen to the recombinant protein structure had distinct effects on the protection generated, compared to that of the trivalent counterparts, depending on the antigen tested.
Highlights
Despite many years of research, toxoplasmosis, like other parasitic invasions, still lacks specific immunoprophylaxis suitable for humans
The main obstacle is the selection of appropriate antigenic composition that is capable of inducing strong protective immunity and a delivery system to ensure its efficient presentation to the immune system
The results of this work emphasize several important points connected to the design of an efficient anti-T. gondii vaccine
Summary
Despite many years of research, toxoplasmosis, like other parasitic invasions, still lacks specific immunoprophylaxis suitable for humans. Usually asymptomatic in otherwise healthy immunocompetent individuals, T. gondii infection can pose a serious threat to health and life in individuals with weakened (AIDS patients, transplant recipients or those receiving immunosuppressive therapy) or underdeveloped (fetuses) immune systems. It is considered clinically asymptomatic, chronic toxoplasmosis may be associated with development of very serious life-controlling neurologic disorders and illnesses, such as schizophrenia [6] or depression [7]. It has been proved in animal models—in particular, in rodents (mice and rats)—that the presence of the parasite within the central nervous system results in highly specific changes in the behavior of the intermediate host that are believed to increase the likelihood of the parasite’s transmission to the definitive hosts, which are felids
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