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Importance of proliferation and recirculation of effector memory CD8+ t cells for the success of genetic vaccination using the heterologous prime-boost regimen


CD8 + T lymphocytes restricted to the major histocompatibility complex molecules Ia are important to host survival of the after viral, bacterial, fungal or parasitic infections. Based on this knowledge, it is believed that the induction of these cells will be important for the generation of new vaccines. Over the past 20 years, solid evidence demonstrated that the heterologous prime-boost regimen achieves the best results in terms of the induction of long-lived protective effector memory CD8 + T cells against several experimental infections. Although this regimen is being used more and more often, as is the case for many vaccines, the mechanisms that support its effectiveness are still largely unknown. Certainly part of its effectiveness depends on the generation and maintenance of a large number of poly-functional specific lymphocytes. However, other specific features can also be important. It will be our goal in this project to study 2 important aspects which may be related to the success of this vaccination strategy. We will test whether after the infectious challenge, the proliferation and re-circulation of T lymphocytes in general, and more specifically CD8+ ones, are critical to the observed protective immunity. To this end, mice will be immunized with recombinant plasmidial DNA followed by a boost with replication deficient human adenovirus type 5 both expressing the protein 2 of the amastigote surface of Trypanosoma cruzi. After challenge with the T. cruzi, we will determine the phenotype and function of specific CD8+ T lymphocytes which proliferate and re-circulate. In order to determine the significance of these events to the protective immunity, we will inhibit the proliferation of lymphocytes by the treatment with hydroxiurea or their re-circulation with the drug FTY-720. We hope that these experiments will determine the phenotype and function of the specific effector memory CD8+ T lymphocytes responsible for mediating protective immunity and the importance of their proliferation and re-circulation for the vaccination success using the heterologous prime-boost regimen. This knowledge is important for the development of more efficient vaccines and to the comprehension of the immunological mechanisms of protection mediated by memory T cells. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VIRGILIO, FERNANDO DOS SANTOS; PONTES, CAMILA; DOMINGUEZ, MARIANA RIBEIRO; ERSCHING, JONATAN; RODRIGUES, MAURICIO MARTINS; VASCONCELOS, JOSE RONNIE. CD8(+) T Cell-Mediated Immunity during Trypanosoma cruzi Infection: A Path for Vaccine Development?. Mediators of Inflammation, . (12/22514-3, 13/13668-0, 09/06820-4)

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