Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

Abstract

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4+ T and CD8+ T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4+ T and CD8+ T cell responses elicited by a specific immunological adjuvant.

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

“…46 The use of T. cruzi-derived TLR agonists as immunological adjuvants also resulted in a significant delay in the growth of the B16-F10 melanoma cell line expressing NY-ESO-1 antigen. 47 Interestingly, protective immunity correlated with the magnitude of CD8 1 T-cell responses induced by a specific TLR agonist. One of the major challenges in the development of an efficient anticancer vaccine is overcoming immune tolerance to tumor-associated antigens (TAA), as well as the active immune evasion strategies developed by tumors.…”

“…In fact, it was found that a recombinant nonpathogenic clone of T. cruzi expressing a cancer testis antigen (NY‐ESO‐1) induces antigen‐specific T‐cell responses and effective protection against tumors in a mouse model . The use of T. cruzi ‐derived TLR agonists as immunological adjuvants also resulted in a significant delay in the growth of the B16‐F10 melanoma cell line expressing NY‐ESO‐1 antigen . Interestingly, protective immunity correlated with the magnitude of CD8 + T‐cell responses induced by a specific TLR agonist.…”

Specific activation of CD4–CD8– double-negative T cells byTrypanosoma cruzi-derived glycolipids induces a proinflammatory profile associated with cardiomyopathy in Chagas patients

“…Because of its role in activating the immune response, GPI mucins and GIPLs are being used as adjuvants in immunization protocols against T. cruzi, with the hope of finding effective vaccines [54]. Because of its role in activating the immune response, GPI mucins and GIPLs are being used as adjuvants in immunization protocols against T. cruzi, with the hope of finding effective vaccines [54].…”

Immunological Processes in Cancer: A Link Between Inflammation and Immunity

“…Thus, Junqueira et al (2012) used a melanoma mouse models to investigate the role of antigens derived of plasmatic membrane of the Trypanosoma cruzi as immunological adjuvants in an antitumor vaccine. Obtaining favorable results, the antigens of Trypanosoma cruzi were considered an efficient immunological adjuvant.…”