Novel Concepts in Using Broadly Neutralizing Antibodies for HIV-1 Treatment and Prevention

Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication and preventing disease progression, the high costs, the burden of daily medication, toxicity and the development of resistance underscore the need for new therapeutic approaches. Over the past decade, broadly HIV-1 neutralizing antibodies (bNAbs) were discovered that are up to a 1000-fold more potent than HIV-1-reactive antibodies previously described. About 10 years after the first identification of these broadly neutralizing antibodies, bNAbs that effectively target multiple HIV-1 variants with a high potency have been found for most of the immunological important epitopes on the HIV-1 envelope-trimer like the CD4 binding site, the V1/V2 loop, the V3-glycan, the membrane-proximal external region (MPER), the interface region with the fusion peptide and the so called ‘silent face’. Some of these bNAbs have been demonstrated to safely suppress viremia and delay viral rebound after interruption of antiretroviral therapy (ART) in HIV-1-infected individuals. Moreover, bNAbs have been demonstrated to prevent infection in animal models and prevention studies where bNAbs are tested for their effectivity as passive immunization in humans are currently ongoing. Thus, bNAbs represent a promising novel approach for effective HIV-1 immunotherapy and prevention. However, infusions of single bNAbs drive the emergence of viral escape mutations and some patients harbor pre-existing resistance in their proviral or circulating HIV-1 quasispecies. Furthermore, the recently completed proof-of-concept Antibody Mediated Prevention (AMP) phase 2b trials showed that much higher bNAb titers or more potent and broader bNAbs, especially for single bNAbs, would be required for HIV-1 prevention in real-world settings. Thus, in order to restrict HIV-1 escape mechanisms and for improved antibody-mediated HIV-1 prevention, future regimens will require novel antibodies, antibody combinations or novel concepts like e.g. bi- or trispecific antibodies. In this Research Topic, we aim to bring together new studies and comprehensive reviews that advance the field of bNAbs and their future clinical use for treatment and prevention of HIV-1.