Experimental COVID-19 vaccine prevents severe disease in mice
Vaccine prevents pneumonia, elicits high levels of protective antibodies


Date:
August 12, 2020
Source:
Washington University School of Medicine
Summary:
Researchers have created a COVID-19 vaccine candidate from a
replicating virus. This experimental vaccine has proven effective
at preventing pneumonia in mice.



FULL STORY ==========================================================================
An experimental vaccine is effective at preventing pneumonia in mice
infected with the COVID-19 virus, according to a study from Washington University School of Medicine in St. Louis. The vaccine, which is made
from a mild virus genetically modified to carry a key gene from the
COVID-19 virus, is described in the journal Cell Host and Microbe.


========================================================================== "Unlike many of the other vaccines under development, this vaccine is
made from a virus that is capable of spreading in a limited fashion
inside the human body, which means it is likely to generate a strong
immune response," said co- senior author Michael S. Diamond, MD, PhD,
the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. "Since the virus is capable
of replicating, it can be grown to high levels in the lab, so it's easy to scale up and should be more cost-effective than some of the other vaccine candidates. So while what we have shown is just the proof of concept,
I think it's very promising. Our vaccine candidate is now being tested in additional animal models with the goal of getting it into clinical trials
as soon as possible." Diamond and colleagues -- including co-senior
author Sean Whelan, PhD, the Marvin A. Brennecke Distinguished Professor
and head of the Department of Molecular Microbiology; and co-first authors Brett Case, PhD, a postdoctoral researcher in Diamond's laboratory,
and Paul W. Rothlauf, a graduate student in Whelan's laboratory --
created the experimental vaccine by genetically modifying vesicular
stomatitis virus (VSV), a virus of livestock that causes only a mild, short-lived illness in people. They swapped out one gene from VSV for
the gene for spike from SARS-CoV-2, the virus that causes COVID-19. The
hybrid virus is called VSV-SARS-CoV-2.

Spike protein is thought to be one of the keys to immunity against
COVID-19.

The COVID-19 virus uses spike to latch onto and infect human cells,
and the human body defends itself by generating protective antibodies
targeting spike.

By adding the gene for spike to a fairly harmless virus, the researchers created a hybrid virus that, when given to people, ideally would elicit antibodies against spike that protect against later infection with the
COVID-19 virus.

The same strategy was used to design the Ebola vaccine that was approved
by the U.S. Food and Drug Administration in 2019. That vaccine -- which
is made from VSV genetically modified with a gene from Ebola virus --
has been safely administered to thousands of people in Africa, Europe
and North America, and helped end the 2018 to 2020 Ebola outbreak in
the Democratic Republic of the Congo.

As part of this study, the researchers injected mice with VSV-SARS-CoV-2
or a lab strain of VSV for comparison. A subgroup was boosted with a
second dose of the experimental vaccine four weeks after the initial injections. Three weeks after each injection, the researchers drew blood
from the mice to test for antibodies capable of preventing SARS-CoV-2 from infecting cells. They found high levels of such neutralizing antibodies
after one dose, and the levels increased 90-fold after a second dose.

Then, the researchers challenged the mice five weeks after their last
dose by spraying the COVID-19 virus into their noses. The vaccine
completely protected against pneumonia. At four days post infection,
there was no infectious virus detectable in the lungs of mice that
had been given either one or two doses of the vaccine. In contrast,
mice that had received the placebo had high levels of virus in their
lungs. In addition, the lungs of vaccinated mice showed fewer signs of inflammation and damage than those of mice that had received the placebo.

The experimental vaccine is still in the early stages of development.

Mice do not naturally become infected with the COVID-19 virus, so to
assess whether the vaccine elicited a protective immune response in
them, the researchers used genetically modified mice or, in unmodified
mice, employed a complicated technique to induce susceptibility to
infection. The researchers are in the process of repeating the experiments
in other animal models that are naturally susceptible to the COVID-19
virus. If the vaccine also protects those animals from COVID-19, the
next step would be to scale up production under what the Food and Drug Administration refers to as "good manufacturing practice (GMP) conditions"
and launch a clinical trial in people.

While the data are promising, this vaccine is still months behind in
the race to develop a pandemic-ending vaccine. Six vaccines are in the
final stage of testing in people, and Anthony Fauci, MD, director of the
U.S. National Institute of Allergy and Infectious Diseases, has said he
expects a vaccine to be ready for mass distribution early next year.

"It's really going to depend on how successful the first vaccines that
come out for COVID are," Whelan said. "If they don't produce a robust,
durable immune response or there are safety issues, there might be the opportunity for a second-generation vaccine that could induce sterilizing immunity and interrupt the cycle of transmission."

========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. James Brett Case, Paul W. Rothlauf, Rita E. Chen, Natasha M. Kafai,
Julie
M. Fox, Brittany Smith, Swathi Shrihari, Broc T. McCune, Ian
B. Harvey, Shamus P. Keeler, Louis-Marie Bloyet, Haiyan Zhao,
Meisheng Ma, Lucas J.

Adams, Emma S. Winkler, Michael J. Holtzman, Daved H. Fremont,
Sean P.J.

Whelan, Michael S. Diamond. Replication-competent
vesicular stomatitis virus vaccine vector protects against
SARS-CoV-2-mediated pathogenesis in mice. Cell Host & Microbe,
2020; DOI: 10.1016/j.chom.2020.07.018 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200812094913.htm

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