naa a22 4500 530045990 CHVBK 20181024071132.0 cr unu---uuuuu 181024e20181001xx s 000 0 eng 10.1172/JCI99005 doi (SERVAL)BIB_A76F3B73E54A 30148455 pmid 000446063600025 isiid TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs [Elektronische Daten] [L. Cheng, Q. Wang, G. Li, R. Banga, J. Ma, H. Yu, F. Yasui, Z. Zhang, G. Pantaleo, M. Perreau, S. Zurawski, G. Zurawski, Y. Levy, L. Su] Activation of HIV-1 reservoirs and induction of anti-HIV-1 T cells are critical to control HIV-1 rebound after combined antiretroviral therapy (cART). Here we evaluated in humanized mice (hu-mice) with persistent HIV-1 infection the therapeutic effect of TLR3 agonist and a CD40-targeting HIV-1 vaccine, which consists of a string of 5 highly conserved CD4+ and CD8+ T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol fused to the C-terminus of a recombinant anti-human CD40 antibody (αCD40.HIV5pep). We show that αCD40.HIV5pep vaccination coadministered with poly(I:C) adjuvant induced HIV-1-specific human CD8+ and CD4+ T cell responses in hu-mice. Interestingly, poly(I:C) treatment also reactivated HIV-1 reservoirs. When administrated in therapeutic settings in HIV-1-infected hu-mice under effective cART, αCD40.HIV5pep with poly(I:C) vaccination induced HIV-1-specific CD8+ T cells and reduced the level of cell-associated HIV-1 DNA (or HIV-1 reservoirs) in lymphoid tissues. Most strikingly, the vaccination significantly delayed HIV-1 rebound after cART cessation. In summary, the αCD40.HIV5pep with poly(I:C) vaccination approach both activates replication of HIV-1 reservoirs and enhances the anti-HIV-1 T cell response, leading to a reduced level of cell-associated HIV-1 DNA or reservoirs. Our proof-of-concept study has significant implication for the development of CD40-targeting HIV-1 vaccine to enhance anti-HIV-1 immunity and reduce HIV-1 reservoirs in patients with suppressive cART. Cheng L. aut Wang Q. aut Li G. aut Banga R. aut Ma J. aut Yu H. aut Yasui F. aut Zhang Z. aut Pantaleo G. aut Perreau M. aut Zurawski S. aut Zurawski G. aut Levy Y. aut Su L. aut The Journal of clinical investigation 128/10(2018-10-01), 4387-4396 128:10<4387-4396 2018 128 1 article serval SERVAL 700 1- Cheng L. aut SERVAL 700 1- Wang Q. aut SERVAL 700 1- Li G. aut SERVAL 700 1- Banga R. aut SERVAL 700 1- Ma J. aut SERVAL 700 1- Yu H. aut SERVAL 700 1- Yasui F. aut SERVAL 700 1- Zhang Z. aut SERVAL 700 1- Pantaleo G. aut SERVAL 700 1- Perreau M. aut SERVAL 700 1- Zurawski S. aut SERVAL 700 1- Zurawski G. aut SERVAL 700 1- Levy Y. aut SERVAL 700 1- Su L. aut SERVAL 773 0- The Journal of clinical investigation 128/10(2018-10-01), 4387-4396 128:10<4387-4396 2018 128 BK010053 XK010053 XK010000 SERVAL SERVAL SERVAL article