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Highlight | News | Scientific result | Vaccine | Infectious diseases | Immune system
A study led by IMVA-HB/IDMIT researchers, published in NPJ Vaccines, has shown the influence of the delay between vaccinations (primary and booster) on the specific humoral immune response. This work also suggests the establishment of a trained immune memory.
Vaccines represent one of the greatest successes in
medicine, reducing mortality and morbidity associated with many infectious
diseases. Thanks to vaccines and effective global vaccination campaigns,
pathogens can be eradicated from the planet, as was the case with the smallpox
virus in the 1980s, and will be the case in the near future - as hoped for with
the polio virus. According to the World Health Organization, vaccinations save
the lives of 2 to 3 million people worldwide every year.
However, we still don't have vaccines against certain
diseases such as AIDS, and the development of a vaccine is an extremely long
process that is ill-suited to deal with emerging diseases.
Vaccine research aims not only to develop new vaccines, but
also to improve the comfort, tolerance and efficacy of existing vaccines. It is
expected that a better understanding of the mode of action of vaccines that
work would allow for a more rational, faster development of new vaccines,
improve current vaccination protocols, and personalize vaccinations.
With this goal in mind, a team of vaccinologists from
IMVA-HB/IDMIT has analyzed the dynamics of innate and acquired immune responses
and their interactions after primary and booster vaccination. To do this, they
vaccinated monkeys with a live, highly attenuated vaccine, MVA (Modified
Vaccinia Ankara). The model vaccine, MVA, is a vaccine that protects against
smallpox and is showing encouraging results as a recombinant vaccination vector
against other diseases when it expresses their antigens. Because of their
phylogenetic proximity to humans, non-human primates, such as the macaque
monkey, provide strong pre-clinical models for studying the immunology of human
By comparing different vaccination schedules with a
two-month or two-week booster vaccination, they have demonstrated the influence
of the delay between vaccinations on the antibody response. While it may be
tempting to shorten the vaccination schedule to provide more rapid protection
of the population at risk in the event of a public health emergency against a
pandemic, an accelerated vaccination schedule has been shown to be detrimental
to humoral immunity.
They have also shown that the vaccination schedule also has
an impact on innate response. The later booster (at two months) not only
improved the specific antibody response of the MVA vaccine, it also involved
more activated and mature innate cells as shown by complex phenotypic analysis
in mass cytometry. Neutrophils, monocytes and dendritic cells with altered phenotype,
better equipped to respond to new stimulation, were induced late after primary
vaccination and their abundance correlated positively with antibody
concentration and multifunction.
This work suggests the development of an innate immune
memory, also called trained immunity1 , which has recently been described for
monocytes and NK cells, and whose mechanisms and characteristics differ from
the "classical" memory of T and B lymphocytes. This remains to be
demonstrated by functional analysis. Most importantly, they reveal the major
effect of the delay between immunizations on vaccine response and highlight the
link between innate, early but also late response and humoral response.
Vaccines based on trained immunity could combine the
induction of innate and adaptive immune memory and thus confer better
protection against the pathogen they target, but also against other pathogens,
and increase and modulate responses to re-vaccination or new independent
vaccinations. This involves identifying vaccines and adjuvants capable of
stimulating innate memory and deciphering the underlying mechanisms to better
1: Unlike adaptive memory, innate myeloid memory is not
antigen-specific. It is carried by monocytes with improved antimicrobial
functions against stimuli that have nothing to do with the initial inducing
stimulus. Thus, BCG, the canonical stimulus of innate memory, protects more
than against tuberculosis. Furthermore, trained immunity does not appear to
involve clonal expansion of monocytes and their differentiation into monocyte
memory, but metabolic, epigenetic, and transcriptional changes in hematopoietic
progenitors/precursors generating trained monocyte progeny.
Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations I NPJ Vaccines
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