Gras – Viral and structural immunology
Our laboratory is focused on understanding how to combat viral infections.
Viruses are part of day-to-day encounters that our immune system needs to deal with. How the immune system “sees”, recognises and eliminates viral infection is not fully understood.
Indeed, viruses are able to mutate in order to escape the immune system surveillance. If we were to develop better vaccine and drugs, it is essential to understand the mechanism of viral recognition and viral escape prior to this.
Our lab combines both the cellular and structural approaches to understand the immune system action when face with a viral infection.
Our research on Influenza virus
Influenza viruses cause significant morbidity and mortality worldwide. Although a vaccine is available, it primarily induces a humoral response and requires updating annually. Additionally, the vaccine provides protection if the predicted strains match the circulating strains but sometimes the virus mutate away from the prediction and the vaccine will have minimal benefit. There is a need and effort to develop a universal influenza vaccine that could provide long-lasting protection against distinct influenza strains throughout global populations. This will allow a one-short vaccine to be developed, that would protect against multiple strains of the virus without the need of having to predict every year or having to update the vaccine and get the “jab” every year. Our immune system is arm of cells called CD8+ T cells that are known to be protective against influenza disease, decreasing the quantity of virus (viral load) and disease severity.
Our aim is to understand how we can isolate T cells that would be protective, identify their characteristics and provide the information to understand how we can specifically activate those cells. Our lab has multiple projects focused on understanding the influenza virus immunity:
- Understanding how some T cells are able to recognise multiple mutations within the same epitope, enabling the immune system to protect us against different flu strains.
- Discovering new flu epitopes that are activating potent T cells across individuals with different genetic
- Determining the mode of action of drugs that target influenza.
Our research on HIV virus
While antiretroviral therapy (ART) has dramatically improved the health of HIV-infected individuals, comorbidities associated with persisting inflammation (e.g. cardiovascular disease, osteoporosis, cancer) have emerged as important complications. It is unquestionable and imperative to develop new treatments (and ideally, a vaccine) for this virus. Therapeutics or vaccine that could control HIV would help avoid damage by comorbidities. Unfortunately, there are major hurdles imposed by HIV (i.e. high mutation and replication rates creating tremendous viral diversity and the latent HIV reservoir established after infection) that are difficult to overcome.
To tackle these issues our work will focus on a subset of individuals – named controllers – known to control HIV infection and/or delay disease progression. Although HIV infection impacts on multiple facets of the immune system (including T cells, Natural Killer cells, Treg cells, among others), the strongest genetic links to HIV control shown to date have been the expression of specific “protective” human leukocyte antigen (HLA) molecules and their associated potent T cell responses. Understanding such superior T cell responses at the molecular level—specifically, the interaction between HIV peptides presented by HLA complexes and T cell receptors —is central for informing therapeutic or vaccine development against HIV.
Our aim is to understand how HIV controllers T cells are protective, their functional but also molecular features, that could provide some information for new therapeutic avenues.