Francis Crick Institute scientists have discovered unexpected ways in which age and a particular type of immune cell make-up affect how an individual responds to vaccination, giving us clues as to how we might improve our immune responses to other forms of treatment, for example cancer immunotherapy.
In a study carried out by Professor Adrian Hayday (currently based at the Crick’s Lincoln’s inn Fields Laboratory) and colleagues, 178 healthy participants were immunised with a vaccine for ‘swine flu’- caused by a type of influenza virus (H1N1) that circulated in a major outbreak in 2009 – that contained an additional compound, called an adjuvant, designed to boost immune responses. The team then measured tens of thousands of parameters that affect the responsiveness of the immune system in humans.
They found that within less than one day, volunteers showed profound changes in the frequencies of circulating white blood cells, as well as in the genes and proteins expressed by these cells, compared with their pre-vaccination state. However, they unexpectedly found that the nature of this early immune response was different in younger volunteers (up to 35 years of age) versus older volunteers.
Although it is well-known that vaccination can cause temporary discomfort in some individuals, those adverse outcomes have never previously been linked to a component of the immune response. About 30 of the participants in Professor Hayday’s study reported adverse responses, and in many of these the authors detected an increased numbers of immature B cells, also known as transitional B cells, that were present even before the vaccination. B cells are responsible for making antibody molecules, and transitional B cells have previously been associated with autoimmune diseases that affect joints or connective tissues. Following this line of reasoning, the authors found, most unexpectedly, that autoantibodies were often present pre-vaccination in the blood of those making adverse responses to vaccination, despite their being otherwise healthy subjects. These findings offered a novel linkage between the immune system and the likelihood of making adverse responses that might help our understanding of why different patients respond very differently to cancer immunotherapies.
Professor Hayday explained: “Essentially everyone inoculated in this study developed some form of an immune response within 24 hours. Of note, this strong and rapid response included the mobilisation of lymphocytes that the textbooks tell us are only likely to react around one week after vaccination. This is a clear example of what we learn from studying humans directly. Surprisingly, this early response began to differ in people in their thirties and over. This again is not predicted by the textbooks and is a sharp reminder that age is going to be an important factor in how people respond to vaccines and immunotherapies.
“Most unexpectedly, individuals with a particular type of immune cell – an atypical B cell – were more likely to experience pain or fever or joint ache following vaccination. Such a linkage of immunological metrics to how people feel – so-called “Man-Flu”- has not previously been shown. Indeed the study shows that Man-Flu was real for about one fifth of those participating in the study, and was no more frequent in men than in women.
“While outcomes will vary from vaccine to vaccine and from vaccine to other forms of immunotherapy, these insights may help identify those people most likely to feel unwell following vaccination and perhaps following cancer immunotherapy. The insights should also aid the better design of vaccines. At the same time, it is important to note that those who felt unwell after the vaccine rapidly recovered and there was not a shred of evidence that the vaccination provoked any lasting harm. By contrast, it rapidly induced strong antibody responses against swine flu in 80% of those immunised.”
The paper, Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events, is published in Nature Immunology.