The complex relationship between viruses and our immune system

 Virus Appreciation Day, celebrated annually on 3 October, serves a dual purpose: to foster respect and understanding for viruses while raising awareness about their serious impacts on health. To mark the day, Professor John Tregoning from Imperial’s Department of Infectious Disease shares valuable insights into influenza viruses, highlighting their effects, the importance of vaccination, and ongoing research for universal vaccines against evolving strains in our latest blog.

Viruses have an enormous impact on human health, but they don’t only infect humans. Many viruses also infect animals, plants and even bacteria. Some viruses are quite promiscuous, infecting a wide range of animal species before passing on to humans through a process known as zoonotic transmission. One of the most problematic of these zoonotic infections is influenza virus.

The main natural reservoir of influenza virus is wild birds, particularly ducks and geese. The virus can then transmit from these birds into domestic poultry, like chickens, and to livestock, such as pigs, before ultimately reaching people. In the past five years, a new strain of avian influenza has emerged with an ability to infect an even wider range of mammalian species. It has been detected in cattle in the US.

Influenza, the disease caused by the virus, poses a substantial health burden. It resulted in nearly 15,000 deaths in the UK in the 2022-23 winter season. As well as death, it is a significant cause of hospitalisation and general illness – with a long tail of recovery. Additionally, influenza infection doubles the risk of heart attacks and strokes for up to a year after illness. Given these risks, getting an influenza vaccine this time of year is highly recommended. As I discovered researching my latest book Live Forever one of the simplest ways of extending your life is through vaccination. A vaccine will give you protection against the most severe forms of disease caused by the virus and protect you against subsequent illness.Vaccines train your body to recognise pathogens and fight them off. To do this, they make use of a facet of immunity called immune memory. When re-exposed to the same virus, your immune response activates faster and stronger, stopping the infection in its tracks. Several aspects of immune memory can prevent subsequent infections, but an important one are antibodies – this is a type of protein that is highly specific in what it can recognise and bind. When you are immunised with influenza vaccine, you make influenza virus specific antibodies that can stop the virus from infecting you.

However, influenza virus is a tricky customer. It changes its coat in an attempt to escape antibodies and this means that the vaccine can become outdated – necessitating boosters each year. These different types of virus are called different strains. A huge goal in influenza vaccine research is to make a vaccine that can recognise a wider range of different influenza virus strains, even as they mutate to evade the immune response. These are called universal influenza vaccines; ideally you would be able to have a single immunisation and get lifelong protection.

But there are a number of potential hurdles in the path to developing such a vaccine, these relate to the virus itself, but also how our immune system works and forms memory. One facet of the immune response that we have been investigating recently is called ‘original antigen sin’ – which is not a particularly catchy name. What it refers to is how the first exposure to a series of similar looking viruses affects subsequent responses. It’s a bit like how babies learn to recognise people – the first woman a baby recognises might be called mummy and subsequently they might refer to all women as mummy (at least for a while). In the case of original antigen sin, the immune system may focus on familiar elements of different viruses at the expense of recognising new or changing parts, leading to inefficiencies in responding to variations.

 The problem with studying this is that human’s exposure to influenza is extremely complex – we have all been infected at different times with different viruses, some of us will then mix this up with a vaccination leading to a natural history of disease that is very hard to interpret. In our most recently published work in The Journal of Infectious Disease, we used a different approach to understand the immune response to influenza infection. Through a collaboration with the pharmaceutical company Sanofi, we performed experiments on a type of mouse called the Kymouse that has been genetically engineered to make human like antibodies. This allowed us to explore how antibodies change following infections with different strains of influenza virus. Our studies suggested that infection with one strain can affect the response to a subsequent infection.

Want to Learn more?

This complex interplay of virus and human immune response is an endlessly fascinating subject, unlocking its secrets can help us identify new ways to protect humans (and chickens) from infection with a deadly virus. But don’t restrict yourself to learning about it on Virus Appreciation Day – if you have found your appetite whetted – why not try our FREE massive open online course called Foundations in Virology and Vaccinology. It does exactly what it says in the link, giving an overview of viruses and vaccines, what we know about them and what we hope to discover.