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. The main aim of this project is to study the effect of ART-treated HIV infection on the immunity gained from previously administered vaccines as well as the induction of immunity upon new vaccination. The various study outcomes explore antigen-specific antibody responses and antigen-specific T-cell responses. Transcriptome analysis of antigen-specific T-cells allows for a deeper understanding of how HIV infection alters antigen-specific responses. The relationships between inflammation, the microbiome and antigen-specific responses are explored for in depth understanding of the mechanisms driving vaccine-induced immunity in immunocompromised settings.
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 Sub-Saharan Africa, that has the majority of persons living with HIV, infants are recurrently at risk for various illnesses. The proposed project seeks to unravel the immunological impact of recurrent childhood infections in HIV-exposed uninfected and to assess effects on vaccine immune responses. This DFG-funded project takes place in Cameroon in collaboration with Dr. Livo Esemu and Dr. Micheal Besong.
As cure of HIV-1 infection requires the eradication of viral reservoirs, cure strategies should include boosting of cytotoxic T lymphocytes (CTL) to eliminate infected cells. HIV-1 can evade CTL recognition by Nef-mediated down-regulation of HLA-A/B-expression and Vpu-mediated downregulation of HLA-C. This could explain the failure of T cell-based vaccines to prevent HIV‑1 infection and to improve control of viremia. The negative effect of Nef on CTL epitope presentation varies between the various CTL epitopes as Nef-mediated down-regulation of HLA-A/B is not complete. Own experiments demonstrated that some viral peptides are “resistant” to the negative effects of Nef, as they are still presented to CTL despite low HLA-I expression presumably due to highly efficient processing of the peptides from viral proteins and high binding affinity to the HLA molecules.
In our research project, we are investigating the induction of HIV-1-specific CTL targeting Nef/Vpu-“resistant” CTL epitopes which are still presented to CTL despite the negative effects of Nef and Vpu. For this purpose, we have developed techniques allowing the efficient mapping of Nef/Vpu-“resistant” epitopes. Furthermore, we will analyze whether the recognition of such epitopes correlates to a better suppression of HIV-1 replication and to a better course of HIV-1-infection. The results of this project shall contribute to the development of more efficient HIV-1 vaccines and immunotherapies.