COVID-19 replicating RNA vaccine has robust response in nonhuman
primates

Date:
July 20, 2020
Source:
University of Washington Health Sciences/UW Medicine
Summary:
A replicating RNA vaccine, formulated with a lipid-based
nanoparticle emulsion, produces antibodies against the COVID-19
coronavirus in mice and primates with a single immunization. These
antibodies potently neutralize the virus in young and old
animals. The antibody levels induced are comparable to those in
recovered COVID-19 patients. This formulation is shelf-stable,
with mass-production and distribution advantages.



FULL STORY ==========================================================================
A replicating RNA vaccine, formulated with a lipid-based nanoparticle
emulsion that goes by the acronym LION, produces antibodies
against the COVID-19 coronavirus in mice and primates with a single immunization. These antibodies potently neutralize the virus.


==========================================================================
The effects occurred within two weeks after administration through
injection into a muscle. The level of antibodies generated was comparable
to those in people who are recovering from COVID-19.

The vaccine induced coronavirus-neutralizing antibodies robustly in both younger and older mice. This hopeful finding was well-received by the researchers, because of the concern that the elderly are less likely to
respond to vaccination due to their aging immune systems.

Vulnerability to severe COVID-19 in older people increases with age;
a vaccination suitable for this high-risk population is a key goal of
the scientists.

This vaccine design, as shown in lab studies, is designed to avoid
immune responses that could enhance a respiratory disease induced by
the coronavirus.

Instead, it directs the immune response toward more protective antiviral measures. In addition to antibody production that can block the infection,
the vaccine induces T cells, a type of white blood cell that provides a
second line of defense if antibodies don't completely block the infection.

The methods and results of animal tests of the replicating RNA coronavirus vaccine candidate vaccine are published July 20 in Science Translational Medicine.



==========================================================================
The lead author of the paper is Jesse H. Erasmus, a Washington Research Foundation Postdoctoral Fellow in the laboratory of Deborah Heydenberg
Fuller.

She is a professor of microbiology at the University of Washington School
of Medicine and division chief of Infectious Diseases and Translational Medicine at the Washington National Primate Research Center.

As COVID-19 continues to spread, the discovery and widespread distribution
of safe and effective vaccines are essential for slamming down the
pandemic.

Scores of vaccine candidates are in various stages of testing around
the world, from preclinical studies to human trials.

"A vaccine that can stop COVID-19," Fuller wrote, "will ideally induce protective immunity after only a single immunization, avoid immune
responses that could exacerbate virus-induced pathology, be amenable to
rapid and cost- effective scale-up and manufacturing, and be capable of inducing immunity in all populations including the elderly who typically respond poorly to vaccines." "That's a tall order," she added. She
sees conventional nucleic acid vaccines as promising, but at least two immunizations are needed to instill immunity in people.

Most DNA vaccines require high doses to achieve protective levels of
immunity in humans. Traditional messenger RNA vaccines formulated with
lipid nanoparticles to increase their effectiveness may face obstacles
of mass- production and shelf life.



==========================================================================
To try to overcome these limitations, the labs of Fuller and her
collaborators at the National Institutes of Health Rocky Mountain
Laboratories and HDT Bio Corp. have developed a replicating RNA version
of a coronavirus vaccine.

Replicating RNA vaccines for other infectious diseases and cancers are
in the pipeline at several institutions.

Replicating RNA expresses a greater amount of protein, and also triggers
a virus-sensing stress response that encourages other immune activation.

In the case of the COVID-19 vaccine candidate, the RNA enters cells
and instructs them to produce proteins that teach the body to recognize coronaviruses and attack them with antibodies and T cells.

This blockade might keep the viruses from fusing to cells and injecting
their genetic code for commandeering cellular activities.

These antibodies induced by the vaccine provide protection by interfering
with the protein machinery on the spikes of the coronavirus.

This replicating RNA vaccine contains the novel Lipid InOrganic
Nanoparticle (LION) developed by Seattle-based biotechnology company
HDT Bio Corp.

"We are pleased with the collaboration with UW to move our RNA vaccine
platform forward," said the company's CEO, Steve Reed.

Amit P. Khandhar, the lead formulation developer, added, "RNA
molecules are highly susceptible to degradation by enzymes. LION is a next-generation nanoparticle formulation that protects the RNA molecule
and enables in vivo delivery of the vaccine after a simple mixing step
at the pharmacy." The nanoparticle enhances the vaccine's ability to
provoke the desired immune reaction, and also its stability. This vaccine
is stable at room temperature for at least one week. Its components
would allow it to be rapidly manufactured in large quantities, should
it prove safe and effective in human trials.

The scientists anticipate that lower and fewer doses would need to be
made to immunize a population.

A key differentiating factor between LION and the lipid nanoparticle
delivery vehicle used in other mRNA COVID-19 vaccines is its ability to
be formulated with mRNA by simple mixing at the bedside.

The two-vial approach enabled by LION allows for manufacturing of the formulation independently from the mRNA component.

The research team is working to advance the vaccine to Phase 1 testing
in people, in which it would be introduced into a small group of healthy volunteers to gather preliminary data on whether it is safe and generates
the desired immune response.

HDT is advancing the replicon RNA with LION vaccine toward clinical
development under the name HDT-301.


========================================================================== Story Source: Materials provided by University_of_Washington_Health_Sciences/UW_Medicine.

Note: Content may be edited for style and length.


========================================================================== Related Multimedia:
*
YouTube_video:_Coronavirus_vaccine_candidate_displays_protective_traits ========================================================================== Journal Reference:
1. Jesse H. Erasmus, Amit P. Khandhar, Megan A. O'Connor, Alexandra C.

Walls, Emily A. Hemann, Patience Murapa, Jacob Archer, Shanna
Leventhal, James T. Fuller, Thomas B. Lewis, Kevin E. Draves,
Samantha Randall, Kathryn A. Guerriero, Malcolm S. Duthie, Darrick
Carter, Steven G. Reed, David W. Hawman, Heinz Feldmann, Michael
Gale Jr., David Veesler, Peter Berglund, Deborah Heydenburg
Fuller. An alphavirus-derived replicon RNA vaccine induces
SARS-CoV-2 neutralizing antibody and T cell responses in mice and
nonhuman primates. Science Translational Medicine, July 20, 2020;
DOI: 10.1126/scitranslmed.abc9396 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200720145911.htm

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