Nasal vaccine against COVID-19 prevents infection in mice
Nasal delivery produces more widespread immune response than
intramuscular injection

Date:
August 21, 2020
Source:
Washington University School of Medicine
Summary:
Scientists have developed a vaccine that targets the SARS-CoV-2
virus, can be given in one dose via the nose and is effective
in preventing infection in mice susceptible to the novel
coronavirus. The investigators next plan to test the vaccine in
nonhuman primates and humans to see if it is safe and effective
in preventing COVID-19 infection.



FULL STORY ========================================================================== Scientists at Washington University School of Medicine in St. Louis have developed a vaccine that targets the SARS-CoV-2 virus, can be given in
one dose via the nose and is effective in preventing infection in mice susceptible to the novel coronavirus. The investigators next plan to
test the vaccine in nonhuman primates and humans to see if it is safe
and effective in preventing COVID-19 infection.


==========================================================================
The study is available online in the journal Cell.

Unlike other COVID-19 vaccines in development, this one is delivered
via the nose, often the initial site of infection. In the new study,
the researchers found that the nasal delivery route created a strong
immune response throughout the body, but it was particularly effective
in the nose and respiratory tract, preventing the infection from taking
hold in the body.

"We were happily surprised to see a strong immune response in the cells of
the inner lining of the nose and upper airway -- and a profound protection
from infection with this virus," said 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. "These mice were
well protected from disease. And in some of the mice, we saw evidence
of sterilizing immunity, where there is no sign of infection whatsoever
after the mouse is challenged with the virus." To develop the vaccine,
the researchers inserted the virus' spike protein, which coronavirus
uses to invade cells, inside another virus -- called an adenovirus --
that causes the common cold. But the scientists tweaked the adenovirus, rendering it unable to cause illness. The harmless adenovirus carries
the spike protein into the nose, enabling the body to mount an immune
defense against the SARS-CoV-2 virus without becoming sick. In another innovation beyond nasal delivery, the new vaccine incorporates two
mutations into the spike protein that stabilize it in a specific shape
that is most conducive to forming antibodies against it.

"Adenoviruses are the basis for many investigational vaccines for
COVID-19 and other infectious diseases, such as Ebola virus and
tuberculosis, and they have good safety and efficacy records, but not
much research has been done with nasal delivery of these vaccines,"
said co-senior author David T. Curiel, MD, PhD, the Distinguished
Professor of Radiation Oncology. "All of the other adenovirus vaccines
in development for COVID-19 are delivered by injection into the arm or
thigh muscle. The nose is a novel route, so our results are surprising and promising. It's also important that a single dose produced such a robust
immune response. Vaccines that require two doses for full protection are
less effective because some people, for various reasons, never receive
the second dose." Although there is an influenza vaccine called FluMist
that is delivered through the nose, it uses a weakened form of the live influenza virus and can't be administered to certain groups, including
those whose immune systems are compromised by illnesses such as cancer,
HIV and diabetes. In contrast, the new COVID-19 intranasal vaccine in
this study does not use a live virus capable of replication, presumably
making it safer.

The researchers compared this vaccine administered to the mice in two ways
- - in the nose and through intramuscular injection. While the injection induced an immune response that prevented pneumonia, it did not prevent infection in the nose and lungs. Such a vaccine might reduce the severity
of COVID-19, but it would not totally block infection or prevent infected individuals from spreading the virus. In contrast, the nasal delivery
route prevented infection in both the upper and lower respiratory tract
-- the nose and lungs - - suggesting that vaccinated individuals would
not spread the virus or develop infections elsewhere in the body.

The researchers said the study is promising but cautioned that the
vaccine so far has only been studied in mice.

"We will soon begin a study to test this intranasal vaccine in nonhuman primates with a plan to move into human clinical trials as quickly as
we can," Diamond said. "We're optimistic, but this needs to continue
going through the proper evaluation pipelines. In these mouse models,
the vaccine is highly protective. We're looking forward to beginning the
next round of studies and ultimately testing it in people to see if we
can induce the type of protective immunity that we think not only will
prevent infection but also curb pandemic transmission of this virus."
This work was supported by the National Institutes of Health (NIH),
grant and contract numbers 75N93019C00062, R01 AI127828, R01 AI130591,
R01 AI149644, R35 HL145242, HHSN272201400018C, HHSN272201200026C, F32
AI138392 and T32 AI007163; the Defense Advanced Research Project Agency,
grant number HR001117S0019; a Helen Hay Whitney Foundation postdoctoral fellowship; and the Pulmonary Morphology Core at Washington University
School of Medicine.

Diamond is a consultant for Inbios, Vir Biotechnology, NGM
Biopharmaceuticals, and on the scientific advisory board of Moderna. The Diamond laboratory has received unrelated funding support from Moderna,
Vir Biotechnology, and Emergent BioSolutions. Diamond, Curiel, Ahmed
Hassan and Igor Dmitriev have filed a disclosure with Washington
University for possible development of ChAd- SARS-CoV-2. Michael
Holtzman is a member of the DSMB for AstroZeneca and founder of NuPeak Therapeutics. The Baric laboratory has received unrelated funding support
from Takeda, Pfizer and Eli Lily.


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


========================================================================== Journal Reference:
1. Ahmed O. Hassan, Natasha M. Kafai, Igor P. Dmitriev, Julie M. Fox,
Brittany K. Smith, Ian B. Harvey, Rita E. Chen, Emma S. Winkler,
Alex W.

Wessel, James Brett Case, Elena Kashentseva, Broc T. McCune, Adam L.

Bailey, Haiyan Zhao, Laura A. VanBlargan, Ya-Nan Dai, Meisheng
Ma, Lucas J. Adams, Swathi Shrihari, Jonathan E. Danis, Lisa
E. Gralinski, Yixuan J. Hou, Alexandra Scha"fer, Arthur S. Kim,
Shamus P. Keeler, Daniela Weiskopf, Ralph S. Baric, Michael
J. Holtzman, Daved H. Fremont, David T.

Curiel, Michael S. Diamond. A single-dose intranasal ChAd
vaccine protects upper and lower respiratory tracts against
SARS-CoV-2. Cell, 2020; DOI: 10.1016/j.cell.2020.08.026 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200821155747.htm

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