Engineered immune cells elicit broad response to HIV in mice, offering
hope for vaccine

Date:
November 19, 2020
Source:
Scripps Research Institute
Summary:
Unlike so many other deadly viruses, HIV still lacks a vaccine. The
virus has proven especially tricky to prevent with conventional
antibodies, in part because it evolves so rapidly in the body. A
solution would require coaxing the body into producing a special
type of antibody that can act broadly to defeat multiple strains of
the virus at once. Scientists have moved closer to attaining that
goal with an approach that would rely on genetically engineered
immune cells from the patient's body.



FULL STORY ========================================================================== Unlike so many other deadly viruses, HIV still lacks a vaccine. The
virus - - which continues to infect millions around the world --
has proven especially tricky to prevent with conventional antibodies,
in part because it evolves so rapidly in the body. Any solution would
require coaxing the body into producing a special type of antibody that
can act broadly to defeat multiple strains of the virus at once.


==========================================================================
This week, scientists at Scripps Research moved closer to attaining that
holy grail of HIV research with a new vaccine approach that would rely
on genetically engineered immune cells from the patient's body.

In experiments involving mice, the approach successfully induced broadly neutralizing antibodies -- also called bnabs -- that can prevent HIV
infection, says principal investigator James Voss, PhD, of Scripps
Research. The study appears in Nature Communications.

Voss and his team showed in 2019 that it was possible to reprogram the
antibody genes of the immune system's B cells using CRISPR so the cells
would produce the same broadly neutralizing HIV antibodies that have
been found in rare HIV patients.

The new study shows that such engineered B cells, after being
reintroduced to the body, can multiply in response to a vaccination --
and mature into memory cells and plasma cells that produce high levels of protective antibodies for long periods of time in the body. The team also demonstrated that the engineered genes can be improved to make antibodies
that are even more effective against the virus, using a process that
normally occurs in B cells that are responding to immunization.

"This is the first time it has been shown that modified B cells can
create a durable engineered antibody response in a relevant animal model,"
Voss explains.

He hopes that his vaccine approach may someday prevent new HIV
infections and possibly offer a functional cure to those who already
have HIV/AIDS. The virus is still prevalent throughout the world, with
an estimated 38 million people with the disease in 2019.

Voss notes that in humans, the starting cells to create the vaccine
could be obtained easily from a simple blood draw, then engineered in
the lab before being reintroduced to the patient. He and his team --
including first author Deli Huang, PhD, Jenny Tran, PhD, Alex Olson, PhD,
and graduate student Mary Tenuta -- are now exploring ways to improve
the technology so that it would be accessible to the greatest number of
people. Because the approach relies on delivering genes to a patient's
own immune cells, this could be a significant challenge.

"People think of cell therapies as being very expensive," Voss
says. "We're doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would
replace daily antiviral therapy."

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


========================================================================== Journal Reference:
1. Deli Huang, Jenny Tuyet Tran, Alex Olson, Thomas Vollbrecht,
Mary Tenuta,
Mariia V. Guryleva, Roberta P. Fuller, Torben Schiffner, Justin R.

Abadejos, Lauren Couvrette, Tanya R. Blane, Karen Saye, Wenjuan Li,
Elise Landais, Alicia Gonzalez-Martin, William Schief, Ben Murrell,
Dennis R.

Burton, David Nemazee, James E. Voss. Vaccine elicitation of HIV
broadly neutralizing antibodies from engineered B cells. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-19650-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/11/201119153938.htm

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