Adjuvants developed using computers boost vaccines
In addition to an antigen, many vaccines also contain substances,
called adjuvants, which stimulate the immune system. By using
computer-aided molecular design and machine learning, a Chinese research
team has now developed two novel broad-spectrum adjuvants that can
significantly amplify the immune response to vaccines. As reported in
the journal Angewandte Chemie, they were able to enhance the effectiveness of immunization against certain forms of cancer in animal models.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Adjuvants amplify and prolong the effect of vaccine immunizations.
Aluminum salts have been successfully used as adjuvants for many
decades. Alternatively, there are oil-in-water emulsions that target
pattern recognition receptors on immune cells. However, older versions
of this type of adjuvant were not effective enough or had troublesome
side effects. Newer versions are well-tolerated and effective but need
to be tailored for every individual vaccine.
By using computer-aided molecular design and machine learning, Bing
Yan, Sijin Liu, and their team at the Research Center for
Eco-Environmental Sciences and the Capital Medical University in
Beijing, as well as the University of Chinese Academy of Sciences in
Beijing and Hangzhou, the Shandong First Medical University &
Shandong Academy of Medical Sciences, and the Guangzhou University, have
now developed two novel adjuvants with broad-spectrum effectiveness
that can significantly boost the immune response to vaccines.
The new adjuvants are designed to bind to toll-like receptors (TLR), a
class of proteins used by dendritic cells to detect the characteristic
molecular patterns of pathogens. If an “enemy” is recognized, the
dendritic cell moves into a lymph node and “presents” its find to the
T-cells. These activated T-cells then multiply and enlist further immune
cells in the fight.
The team identified structural characteristics of the binding sites
on human TLR and developed a collection, a substance library, with 46
different ligands that are compatible with the binding site. The special
twist in this case is that these ligands are anchored to the surfaces
of biocompatible gold nanoparticles. This causes them to be bound more
easily by the TLR. Two of the ligands were found to be especially
effective. Comprehensive in vitro, ex vivo, and in vivo
studies demonstrated that they bind to several different TLR and
increase the activation of dendritic cells, presentation of antigens to
T-cells, and their activation.
Mice treated with tumor-specific antigens plus one of these new
adjuvants demonstrated strong immune responses that suppressed tumor
growth and lung metastases after implantation of specific cancer cells.
Adjuvants further optimized through this method could reduce the
problem of decreasing immunity for current vaccines and perhaps make
booster vaccines unnecessary. Their use in immunotherapy to treat cancer
is also highly promising.
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About the Author
Bing Yan is the
Cheung Kong Scholar Professor at Guangzhou University. He is a fellow of
the Royal Society of Chemistry. His research interests are
environmental impacts on health, drug discovery, nanomedicine, and
nanotoxicology.