The Immunogenic and Immunoprotective Activities of Recombinant Chimeric T. gondii Proteins Containing AMA1 Antigen Fragments

Abstract

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans to overcome the shortcomings of currently used treatment methods and protect all hosts against toxoplasmosis. The current work represents a relatively new approach to vaccine development based on recombinant chimeric Toxoplasma gondii antigens. In the present research, three tetravalent chimeric proteins containing different portions of the parasite’s AMA1 antigen—AMA1domainI-SAG2-GRA1-ROP1L (ANSGR), AMA1domainsII,III-SAG2-GRA1-ROP1L (ACSGR) and AMA1fullprotein-SAG2-GRA1-ROP1L (AFSGR)—were tested for their immunogenic and immunoprotective capacities. All tested proteins were immunogenic, as evidenced by the triggering of specific humoral and cellular immune responses in vaccinated C3H/HeOuJ mice, defined by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although all tested preparations provided partial protection against chronic toxoplasmosis in immunized and T. gondii-challenged mice, the intensity of the generated immunoprotection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen’s structure.

Mining the Proteome of Toxoplasma Parasites Seeking Vaccine and Diagnostic Candidates

“…AMA1, only expressed in the Toxoplasma-tachyzoite stage, has an immunogenicity and high pathogenicity compared to other AMAs [23]. Three tetravalent chimeric proteins containing different portions of the parasite's AMA1 antigen-AMA1 domain I -SAG2-GRA1-ROP1 L (A N SGR), AMA1 domains II , III-SAG2-GRA1-ROP1 L (A C SGR) and AMA1 full protein -SAG2-GRA1-ROP1 L (A F SGR)-were evaluated for their immunogenic and immunoprotective potentialities [132]. All evaluated proteins were immunogenic and triggered specific humoral and cellular immune responses in vaccinated mice.…”

“…However, the intensity of the produced immune protection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen's structure. It has been identified that full length AMA1 can trigger further potent immunity in mice, resulting in significantly increased survival and partial protection against Toxoplasma cyst formation [132]. Furthermore, the full-length AMA1 and two different fragments (AMA1N and AMA1C) have been tested for the detection of IgG and IgM anti-Toxoplasma antibodies in human and mouse immune sera in ELISA assays [133].…”

Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

“…Synthetic B and T cell epitopes of GRA2 can partially protect immunized mice against an ME49 challenge infection [ 62 ]. Chimeric protein vaccine comprising fragments of AMA1 fused to SAG1, GRA2, and ROP1 were assessed, with all of the generated chimeric vaccines conferring decent levels of humoral and cellular immune responses [ 63 ]. Similarly, protein vaccines based on B and Th cell epitopes of T. gondii aspartic protease 3 promoted the production of Th1 cytokines and prolonged survival for as long as 18 days after a challenge infection with the virulent RH strain [ 64 ].…”