Immune control of HIV-1
The human immune system can effectively prevent and control viral infections. While many viruses can be neutralized and eliminated from the human body, other viruses persist after infection. However, they are often controlled throughout the entire human lifespan (e.g. certain herpes viruses like CMV infections). The critical function of the immune response becomes evident in immunocompromised individuals, in which latent and controlled viruses often emerge and can cause severe and potentially fatal diseases. In HIV-1 infection, the immune response is usually insufficient to fully suppress viral replication – resulting in a continuous progress of the HIV disease. However, there are rare cases of patients that continuously control HIV-1 viremia early after infection (e.g. elite controllers) or after stopping an effective anti-retroviral therapy (ART). These examples of so-called post-treatment controllers have gained attention over the last years and indicate that an intervention, like treating with ART, may result in long-term HIV-1 control and functional cure.
While post-treatment controllers are infrequent, strategies may exist that improve the induction of HIV-1 control. For example, in non-human primates (NHPs), early treatment with broadly neutralizing antibodies (bNAbs) seems to support the induction of an effective CD8+ T cell response that fully suppresses viremia. We expect that the immune system provides an armamentarium that is highly effective but needs to be specifically induced or modified to successfully control and prevent HIV-1 infection. It is unlikely that this is possible by only utilizing a single arm of the human immune response (such as only antibodies or only T cells) but rather requires a concerted effort of multiple cellular and humoral immune functions.
It has been widely shown that the human immune response can be successfully exploited to prevent and treat diseases as demonstrated by the development of many vaccines against infectious pathogens. Moreover, recent antibody-based cancer therapies often eliminate malignant cells and can induce adaptive T cell immunity. While the introduction of cancer-immunotherapy increased the number of individuals that control and survive malignant diseases, immune-mediated treatment and prevention of HIV-1 infection are still at the beginning. However, similar principles may exist to fully achieve immune-mediated HIV-1 control.
Taken together, the overall goal of our project is to understand the immunological factors and mechanisms that can successfully suppress HIV-1 infection and viral replication. The improved understanding will be used to successfully use immunological mechanisms in HIV-1 infected individuals or to protect individuals at increased risk from infection. In particular, we want to use the great potential of the cellular and humoral immune response to achieve non-drug long-term control of HIV-1 infection.
