Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

Abstract

A new generation of broad and potent anti-HIV-1 monoclonal antibodies has recently been isolated; co-administration of two such antibodies is shown here to result in rapid and potent suppression of plasma viraemia in five chronically SHIV-infected macaques that lasts for several weeks. Two papers published this week test the new generation of broad and potent anti-HIV1 monoclonal antibodies (mAbs) in primate models with promising results, both concluding that their results strongly encourage the investigation of mAb therapy for HIV-1 in humans. Dan Barouch et al. show that a single infusion of the potent, broadly neutralizing anti-HIV-1 antibody PGT121, as well as various mAb cocktails, suppress the virus to undetectable levels in just a week in SHIV-infected rhesus monkeys. Masashi Shingai et al. report that co-administration of the antibodies 3BNC117 and 10-1074 results in potent suppression of plasma viraemia lasting for several weeks in chronically SHIV-infected macaques. Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS1,2,3,4. However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants5,6,7. A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals8. These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9, 10, 11, 12, 13, 14). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian–human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques15,16. Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4–7 days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3–5 weeks in some long-term chronically SHIV-infected animals with low CD4+ T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected individuals experiencing immune dysfunction.