Tuberculosis vaccine strengthens immune system

Date:
June 15, 2020
Source:
University of Bonn
Summary:
A tuberculosis vaccine developed 100 years ago also makes vaccinated
persons less susceptible to other infections. While this effect
has been recognized for a long time, it is not known what causes it.



FULL STORY ==========================================================================
A tuberculosis vaccine developed 100 years ago also makes vaccinated
persons less susceptible to other infections. While this effect has been recognized for a long time, it is not known what causes it. Together with colleagues from Australia and Denmark, researchers from Radboud university medical center the universities of Nijmegen and Bonn have now presented
a possible answer to this question. Their results are also interesting
against the background of the Covid-19 pandemic: several studies are
currently testing the use of the vaccine in preventing severe disease progression in populations at risk such as hospital staff and elderly individuals. The study is published in the journal "Cell Host & Microbe".


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The BCG vaccine (the abbreviation stands for Bacillus Calmette-Gue'rin)
is the only vaccine that provides effective protection against infections
with the tuberculosis bacterium. Since its first medical application
in 1921, it has been used billions of times. An unexpected side effect
became apparent: vaccinated individuals not only contracted tuberculosis
far less frequently, but also other infections. One example comes
from Guinea-Bissau in West Africa: there, the mortality of vaccinated
newborns was almost 40 percent lower than that of unvaccinated babies
A similar effect has now been observed with other vaccines, almost
exclusively with those based on live pathogens. Experts also speak of
"trained immunity": the capacity of innate immune response to become
more efficient independently of the type of reinfection. However, it is
still largely unknown why this training effect can persist for years,
even long after the immune cells that were circulating in the blood at
the time of vaccination have died. Detailed studies on this topic were
lacking, especially in humans; the current study fills this gap to a
certain extent: "We vaccinated 15 volunteers with the BCG vaccine and administered a placebo to five more people for comparison," explains
Prof. Dr. Mihai Netea from the Radboud university medical center in
Nijmegen, the Netherlands. "Three months later, we took both blood and
bone marrow samples from these individuals." Some striking differences
were found between the two groups. For instance, the immune cells in the
blood of vaccinated individuals released significantly more inflammatory messengers. These so-called cytokines strengthen the effectiveness of
the immune defense; for example, they call on other immune cells for help
and direct them to the site of infection. Moreover, the immune cells of vaccinated individuals showed activity of completely different genes than
in the placebo group, especially those required for cytokine production.

Easier access to genes for infection defense There are many different
types of immune cells in the blood. All of them are produced in the bone marrow. This is where the so-called hematopoietic stem cells grow, the "mothers" of all immune cells. The BCG vaccination also causes long-term changes in their genetic program. "We have found that after vaccination, certain genetic material becomes more accessible, which means that it
can be read by the cells more frequently," explains Prof. Dr. Andreas
Schlitzer from LIMES Institute at the University of Bonn.



========================================================================== Metaphorically speaking, every human cell contains in its nucleus a huge library of tens of thousands of books, the genes. When the cell wants
to produce a certain molecule, for example a cytokine, it looks up its
assembly instructions in the corresponding book. But not all of the books
can be taken out so easily: some are usually under lock and key. The
BCG vaccination now makes some of these books available, probably for
many months or years. These include those that are needed for increased cytokine production. "This explains why the vaccination results in an
enhanced immune response in the long term," said Netea. "This may well
be the basis for the lasting impact of the training effect." Another
aspect is also interesting: most of the released books, i.e. the genes
that become more accessible after the vaccine has been administered,
are additionally controlled by a molecule called HNF. This "hepatic
nuclear factor" ensures that the immune cells use their newly acquired
power prudently, meaning that they only release cytokines when there is actually a pathogen that needs to be attacked. "It may be possible to
use this finding therapeutically to specifically manipulate the trained immunity," explains LIMES researcher Prof.

Schlitzer.

The results are also of interest against the background of the current
Covid-19 pandemic: the researchers hope that a BCG vaccination might
have a positive effect on the disease. Although the trained immune system probably cannot prevent infection with the virus, it may reduce the risk
of a severe course.

This might benefit especially the particularly vulnerable medical staff.

Several large-scale medical studies are currently investigating this
question, among others two at Radboud university medical center Nijmegen,
and another at the University of Melbourne, which is also a partner in
the current project.

However, until the results are available, the WHO does not recommend
mass vaccination with the BCG vaccine, also in order not to jeopardize
the supply in tuberculosis regions. Tuberculosis claims more than one
million victims every year, putting it at the top of the list of the
world's deadliest infectious diseases.

###
Publication: Branko Cirovic, L. Charlotte J. de Bree, Laszlo Groh, Bas
A. Blok, Joyce Chan, Walter J.F.M. van der Velden, M.E.J. Bremmers,
Reinout van Crevel, Kristian Ha"ndler, Simone Picelli, Jonas Schulte-Schrepping, Kathrin Klee, Marije Oosting, Valerie A.C.M. Koeken,
Jakko van Ingen, Yang Li, Christine S.

Benn, Joachim L. Schultze, Leo A.B. Joosten, Nigel Curtis, Mihai
G. Netea und Andreas Schlitzer: BCG vaccination in humans elicits
trained immunity via the hematopoietic progenitor compartment;
Cell Host & Microbe; DOI: 10.1016/ j.chom.2020.05.014 Contact:
Prof. Dr. Andreas Schlitzer Quantitative Systembiologie Life and
Medical Sciences (LIMES) der Universita"t Bonn Tel.: +49 228/73-62847
E-mail: andreas.schlitzer@uni-bonn.de Prof. Dr. Mihai G. Netea Radboud university medical center Nijmegen Tel.: +31 (0)24 361 46 52 E-mail: Mihai.Netea@radboudumc.nl

========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


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Link to news story: https://www.sciencedaily.com/releases/2020/06/200615140855.htm

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