Basic and Translational Research on Vaccine-induced Immunity
Vaccines are seen as the most cost-effective approach to curb the impact of infectious diseases on public health. The immunogenicity and efficacy of vaccines rely on optimal functioning of immune cells. However, in disease setting, various mechanisms lead to suboptimal, sometime deleterious immune responses. Our research aims to unravel the various processes that alter vaccine-induced immunity.
Immunity and vaccine-responses in HIV-exposed uninfected infants
A growing number of newborns are exposed to HIV in utero. Although not infected, these HIV-exposed uninfected infants still have a higher risk of severe infections, infection-related hospitalizations, and death compared to HIV-unexposed uninfected infants. In this DFG-funded collaborative project with Cameroon, we are performing a comprehensive analysis that integrates the rate common childhood infections, the inflammation profile and vaccine-induced antibody and T cell responses in HIV-exposed (HEU) compared to unexposed (HUU) infants. Our project aims to unravel immune factors that contribute to a higher risk of disease in HEU infants.
Interaction between the translocated microbiome and the immune system
Very early on during HIV infection, the virus causes damage to gut tissues with as consequence what is commonly named a ‘leaky gut’. Because of this leaky gut, pieces of microbes can now migrate into the blood circulation – a phenomenon called microbial translocation - and reach a wider array of immune cells and organs to incite even more inflammation. To clarify how microbial translocation drives inflammation, we used sequencing technology to detect any non-human entity in the blood (i.e. the translocated microbiome) and measured inflammation. In the immune cells, we looked at gene expression, which gives a detailed look into how cells are responding to their environment at that particular moment. Our works that includes several HIV-cohorts from Uganda, Canada and the USA, revealed that the composition of the translocated microbiome changes during the course of antiretroviral therapy and identified bacteria that likely drive in increased inflammation during treated HIV infection. The results of this work appeared in the journal Cell (22nd of July 2021, volume 184, issue 15) and opens new avenues as it may help identify a new line of therapeutic targets, namely translocated microbial products, that will help limit chronic inflammation in HIV infection. Ongoing work of our research group further addresses the influence of the translocated microbiome on T cell functions.
Understanding dysfunction of vaccine-induced immunity in disease setting
HIV infection causes profound and often irreversible changes to the innate and adaptive immune system. For example, a permanent state of immune activation as well as depletion and dysfunction of CD4+ T cells that are important regulators of humoral and cellular responses, all contribute to an overall impaired immunity even in ART-treated HIV infection. Here, we aimed to study the effect of ART-treated HIV infection on the immunity gained from vaccines administered prior to HIV infection. Samples from HIV-infected subjects are obtained in collaboration with Prof. Dr. med. Thomas Harrer (Medizinische Klinik 3 – UK Erlangen). Our findings highlight a link between persistent inflammation and loss of T cell mediated immunity. Complementary research on SARS-CoV-2-specific immunity explored among other quality of antibody responses in people with HIV and revealed an effect of HIV infection on antibody responses after vaccination. Next to our work on HIV infection, parallel avenues are currently under exploration in the field of hemato-oncology, where our preliminary work similarly shows impaired induction of antigen-specific responses upon vaccination (collaboration with PD Dr. med. Fabian Müller - Medizinische Klinik 5 – UK Erlangen). In addition, we are exploring whether targeting of distinct cellular pathways may help mitigate the effect of diseases on T cell responses to vaccine antigens.
