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.