Llama 'nanobodies' could hold key to preventing deadly post-transplant infection

Date:
July 22, 2021
Source:
University of Cambridge
Summary:
Scientists have developed a 'nanobody' - a small fragment of a llama
antibody - that is capable of chasing out human cytomegalovirus
(HCMV) as it hides away from the immune system. This then enables
immune cells to seek out and destroy this potentially deadly virus.



FULL STORY ========================================================================== Scientists have developed a 'nanobody' -- a small fragment of a llama
antibody -- that is capable of chasing out human cytomegalovirus (HCMV)
as it hides away from the immune system. This then enables immune cells
to seek out and destroy this potentially deadly virus.


========================================================================== Around four out of five people in the UK are thought to be infected
with HCMV, and in developing countries this can be as high as 95%. For
the majority of people, the virus remains dormant, hidden away inside
white blood cells, where it can remain undisturbed and undetected for
decades. If the virus reactivates in a healthy individual, it does not
usually cause symptoms. However, for people who are immunocompromised --
for example, transplant recipients who need to take immunosuppressant
drugs to prevent organ rejection -- HCMV reactivation can be devastating.

At present, there is no effective vaccine against HCMV, and anti-viral
drugs often prove ineffective or have very serious side-effects.

Now, in a study published in Nature Communications, researchers at
Vrije Universiteit Amsterdam in the Netherlands and at the University
of Cambridge have found a way to chase the virus from its hiding place
using a special type of antibody known as a nanobody.

Nanobodies were first identified in camels and exist in all camelids -- a family of animals that also includes dromedary, llamas and alpacas. Human antibodies consist of two heavy and two light chains of molecules,
which together recognise and bind to markers on the surface of a cell or
virus known as antigens. For this special class of camelid antibodies,
however, only a single fragment of the antibody -- often referred to
as single domain antibody or nanobody -- is sufficient to properly
recognize antigens.

Dr Timo De Groof from Vrije Universiteit Amsterdam, the study's joint
first author, said: "As the name suggests, nanobodies are much smaller
than regular antibodies, which make them perfectly suited for particular
types of antigens and relatively easy to manufacture and adjust. That's
why they're being hailed as having the potential to revolutionise antibody therapies." The first nanobody has been approved and introduced onto
the market by biopharmaceutical company Ablynx, while other nanobodies
are already in clinical trials for diseases like rheumatoid arthritis
and certain cancers.

Now, the team in The Netherlands and the UK have developed nanobodies
that target a specific virus protein (US28), one of the few elements
detectable on the surface of a HCMV latently infected cell and a main
driver of this latent state.

Dr Ian Groves from the Department of Medicine at the University of
Cambridge said: "Our team has shown that nanobodies derived from
llamas have the potential to outwit human cytomegalovirus. This could
be very important as the virus can cause life threating complications in
people whose immune systems are not functioning properly." In laboratory experiments using blood infected with the virus, the team showed that the nanobody binds to the US28 protein and interrupts the signals established through the protein that help keep the virus in its dormant state.

Once this control is broken, the local immune cells are able to 'see'
that the cell is infected, enabling the host's immune cells to hunt down
and kill the virus, purging the latent reservoir and clearing the blood
of the virus.

Dr Elizabeth Elder, joint first author, who carried out her work while at
the University of Cambridge, said: "The beauty of this approach is that it reactivates the virus just enough to make it visible to the immune system,
but not enough for it to do what a virus normally does -- replicating and spreading. The virus is forced to put its head above the parapet where
it can then be killed by the immune system." Professor Martine Smit,
also from from the Vrije Universiteit Amsterdam, added: "We believe our approach could lead to a much-needed new type of treatment for reducing --
and potentially even preventing -- CMV infectious in patients eligible
for organ and stem cell transplants." The research was funded by the
Dutch Research Council (NWO), Wellcome and the Medical Research Council,
with support from the NIHR Cambridge Biomedical Research Centre.

========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
story is licensed under a Creative_Commons_License. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Timo W. M. De Groof, Elizabeth G. Elder, Eleanor Y. Lim, Raimond
Heukers,
Nick D. Bergkamp, Ian J. Groves, Mark Wills, John H. Sinclair,
Martine J.

Smit. Targeting the latent human cytomegalovirus reservoir for
T-cell- mediated killing with virus-specific nanobodies. Nature
Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-24608-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210722112859.htm

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