Journal Article

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Nussenzweig, Michel C., Diskin, Ron, Bournazos, Stylianos, Gruell, Henning, Mouquet, Hugo, Ploss, Alexander, Ravetch, Jeffrey V., Billerbeck, Eva, Labitt, Rachael N., Scheid, Johannes F., Eisenreich, Thomas R., Incesu, Reha-Baris, Seaman, Michael S., Dorner, Marcus, Bieniasz, Paul D., Spatz, Linda A., Bjorkman, Pamela J., Gaebler, Christian, Horwitz, Joshua A., Marcovecchio, Paola M., Halper-Stromberg, Ariel, Klein, Florian, Abadir, Alexander, Zang, Trinity

2012

Overview

Passive immunotherapy with a combination of neutralizing monoclonal antibodies is shown to be effective in suppressing HIV replication in a humanized mouse model. A boost for HIV-1 therapy Broadly neutralizing antibodies to human immunodeficiency virus-1 (HIV-1) are slow to develop and are found in only a fraction of patients, but they can prevent infection and so are of great importance for HIV therapy design. Previous work has shown that the virus can quickly evolve resistance against these antibodies; however, more potent antibodies are now available. Michel Nussenzweig and colleagues therefore re-examined the potential of antibody therapy in 'humanized' mice. They demonstrate that passive immunotherapy with combinations of broadly neutralizing antibodies effectively controls HIV-1 infection. The authors suggest that it is time to re-examine monoclonal antibodies as therapeutics in HIV-1-infected individuals. Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection 1 , 2 . Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time 3 , 4 . However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design 5 , 6 , 7 , 8 , 9 . Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy 10 , 11 , 12 , the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/2152/2153/1291 / 692/699/255/1901 / 692/700/565/1436 / Animals / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - therapeutic use / Antibodies, Neutralizing - immunology / Antibodies, Neutralizing - therapeutic use / Antibody Specificity - immunology / Antiretroviral agents / Antiretroviral drugs / Binding sites / Biological and medical sciences / Care and treatment / Cloning / Control / Development and progression / Disease Models, Animal / Drug therapy / Experiments / Half-Life / Health aspects / Highly active antiretroviral therapy / HIV / HIV antibodies / HIV Antibodies - immunology / HIV Antibodies - therapeutic use / HIV infection / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - virology / HIV-1 - genetics / HIV-1 - growth & development / HIV-1 - immunology / HIV-1 - isolation & purification / Human immunodeficiency virus / Human viral diseases / Humanities and Social Sciences / Humans / Immunization, Passive / Infections / Infectious diseases / letter / Medical sciences / Methods / Mice / Mice, Inbred NOD / Monoclonal antibodies / multidisciplinary / Mutation / Polymerase chain reaction / Protection and preservation / Science / Time Factors / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Viral Load - drug effects