MedicalResearch.com Interview with:
Adrian Egli, MD PhD Research Group leader
Infection Biology Laboratory
Department of Biomedicine
University of Basel and University Hospital Basel
Medical Research: What is the background for this study? What are the main findings?
Dr. Egli: Infections with influenza viruses are associated with a high morbidity and mortality. In particular, people with a weak immune system are at danger for more severe complications. This includes elderly people, pregnant women, patients after transplantation, patients with HIV infection, chronic diseases such as diabetes and many more. In these high-risk groups, annual vaccination is clearly recommended.
However, due to the immunsuppressive condition the immune response to the influenza vaccine is often reduced. The seroconversion rate – a 4-fold antibody titer increase upon vaccination – is one of the key markers for a successful vaccination. In young adults the seroconversion rate is normally >85%; however, in patients with immunosuppression, this can be lower than 40%. Improving vaccine efficacy is one of the key focuses of my research group. We try to understand, how to improve vaccines and better protect the people at the highest risks for influenza-associated complications.
In this study, we could show that an important cytokine, called Interferon lambda, is clearly associated with the vaccine induced antibody response upon influenza vaccination. We could show that genetic polymorphisms, in one of the Interferon lambda gene family (IFNL3), are modulating the expression of this gene. This strongly affects the cross talk between the innate and adaptive immune response in the context of vaccination. We observed that, the more Interferon lambda is present, the lower the antibody response is. People with a lower expression of Interferon lambda had a significant higher response to the vaccine. Therefore, we developed substances to block the effect of Interferon lambda. We could show in vitro, that due to the Interferon lambda blockade, the antibody production was improved.
Medical Research: What should clinicians and patients take away from your report?
Dr. Egli: There are two important aspects from this work for clinicians and patients.
- We should be aware, that a vaccine may not offer a 100% protection against a pathogen e.g. influenza. The immune response to a vaccine is highly complex and similar to a „natural“ infection is dependent on the capability of the immune system to recognize pathogens and mount a potent response. This is very much dependent on genetic polymorphisms – the Interferon lambda signalling cascade is one of them.
- The knowledge on genetic polymorphisms for the outcome of vaccines may offer in the near future the opportunity to highly personalize vaccines. For examples patients at high risk for influenza vaccination could receive a highly adapted vaccination based on their genetic risk profile.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Egli: We certainly have to see if the described genetic polymorphisms are also important in other vaccines e.g. pneumococcal vaccine. Currently, we have planed various conformational trials. We will plan on further develop adjuvants for vaccines based on these important findings.
Adrian Egli, Deanna M. Santer, Daire O’Shea, Khaled Barakat, Mohammedyaseen Syedbasha, Madeleine Vollmer, Aliyah Baluch, Rakesh Bhat, Jody Groenendyk, Michael A. Joyce, Luiz F. Lisboa, Brad S. Thomas, Manuel Battegay, Nina Khanna, Thomas Mueller, D. Lorne J. Tyrrell, Michael Houghton, Atul Humar, Deepali Kumar. IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza. PLoS Pathogens, 2014; 10 (12): e1004556 DOI: 10.1371/journal.ppat.1004556