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Antibody-Mediated Therapy of HIV-1 Infection

Periodic Reporting for period 3 - HIV1ABTHERAPY (Antibody-Mediated Therapy of HIV-1 Infection)

Reporting period: 2019-01-01 to 2020-06-30

Antiretroviral therapy (ART) is effective for treating HIV-1 infection and in reducing the risk of infection when used as pre-exposure prophylaxis. Moreover, classical antiviral drugs are well-established and increasingly available in generic form. However, ART is a daily and life-long medication and side effects and development of resistance occur. Thus novel treatment and prevention strategies are required. Novel broadly neutralizing antibodies (bNAbs) targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation. In this project, we aim to understand how we can exploit the unique potential of antibodies to effectively treat and prevent HIV-1 infection. To this end, we i.) develop strategies to isolate HIV-1 neutralizing antibodies with exceptional activity in vivo, ii.) investigate how these antibodies can be used to overcome HIV-1 escape, and iii.) explore how antiviral immune responses of the infected host can contribute to control HIV-1 replication. Identification of these key components will strongly increase the ability to use broadly neutralizing antibodies to effectively prevent and treat HIV-1 infection.

At the beginning of this project, we have performed an extensive screening of HIV-1-infected individuals to identify patients with exceptional HIV-1 neutralizing activity (so called elite neutralizer). Here we have identified multiple elite neutralizers. Moreover, we have developed advanced techniques to study the HIV-1-directed B cell and antibody response on a single cell level. These new methods have been applied to study selected elite neutralizers. As a result, we identified and characterized novel highly potent bNAbs that effectively target HIV-1. With these bNAbs we have also developed new strategies to effectively control HIV-1 infection in vivo. This work was complemented by investigating HIV-1 host control mechanisms that can be utilized to make antibody-mediated therapy more effective. The results so far have been published in various scientific journals (e.g. Science, Nature, Nature Medicine, PNAS) or are being prepared for publication. More information can be found at https://klein-lab.de/.
See Project achievements 1.1
We don't want to include confidential data of the running project in this section, if it will be published to a broader public.