Role of LFA-1 for protective immunity elicited by heterologous prime-boost vaccination against intracellular parasitic infection (CCR5P.206)

Prime-boost vaccine with DNA plasmid followed by adenovirus 5 is a powerful strategy to elicit specific CD8+T cells which play a key role in protective immunity (PI) against intracellular pathogens, such as Trypanosoma cruzi , the causative agent of Chagas9 disease. Integrins, CAM and chemokine receptors may also play a role in this process. We demonstrated that treatment with anti-LFA-1 antibody, in immunized/infected mice, reverted the PI after experimental systemic infection. The aim of this work was to study the role of LFA-1 and VLA-4 integrins, the ICAM-1 and CCR5 after prime-boost vaccine. In order to study the role of LFA-1 and VLA-4 integrins, A/Sn mice were immunized with prime-boost vaccine. After, they were infected and treated with anti-LFA-1 and/or anti-VLA blocking antibodies. The immunized/infected mice treated with anti-LFA-1 displayed high parasitemia and all did not survive more than 30 days after challenge. Interestingly, treatment with anti-VLA-4 did not alter the protective response and all mice remained alive. In addition, LFA-1 blockage neither diminished the frequency nor compromised capacity of specific CD8+T cells in producing IFN-γ and/or TNF-α. Also, deficient ICAM-1 or CCR5 mice immunized and/or infected did not become susceptible to challenge. We concluded that LFA-1 play a critical role in the protective immune response generated by the vaccination, and by blocking this molecule, the CD8+ T cell migration capacity is likely impaired.