Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.
This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), American National Institutes of Health (grant R21AI118411 to M.B), an unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015-AI424-564) to M.B, the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470) to M.G and the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01058) to J.G.P, a research grant from Gilead Sciences (GLD17-00204 and GLD19-00084) to M.B, GeSIDA and the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD16/0025/0007). The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to M.B and J.G.P (CPII15/00014). The “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan Government to M.G. The Spanish Secretariat of Science and Innovation Ph.D. fellowship to A.A-G (BES-2016-076382), AGAUR-FI-B-00582 Ph.D. fellowship from the Catalan Government to O.BL, and PIF-UAB Ph.D. fellowship from Universitat Autònoma de Barcelona to R.SL.