Hamsters develop protective immunity to COVID-19 and are protected by convalescent sera

Date:
June 22, 2020
Source:
University of Wisconsin-Madison
Summary:
In an animal model for COVID-19 that shares important features
of human disease, scientists show that prior infection with the
SARS-CoV-2 virus provides protection against reinfection, and
treatment with convalescent serum limits virus replication in
their lungs.



FULL STORY ==========================================================================
In an animal model for COVID-19 that shares important features of
human disease, scientists at the University of Wisconsin-Madison, the University of Tokyo and the Icahn School of Medicine at Mount Sinai
show that prior infection with the SARS-CoV-2 virus provides protection
against reinfection, and treatment with convalescent serum limits virus replication in their lungs.


========================================================================== Syrian hamsters, commonly found as pets, have served critical roles in understanding human infectious diseases for decades. The new study, led by Yoshihiro Kawaoka and published today (June 22, 2020) in the Proceedings
of the National Academy of Sciences, demonstrates they are also a useful
small animal model for researchers trying to understand SARS-CoV-2 and in evaluating vaccines, treatments and drugs against the disease it causes.

"Hamsters are good models for human influenza and SARS-CoV," says Kawaoka, professor of pathobiological sciences at the UW School of Veterinary
Medicine and a virology professor at the University of Tokyo. "This is
why we decided to study them with COVID-19. We wanted to see if the
disease course is similar to humans in these animals from beginning
to end." A study led by scientists at the University of Hong Kong,
published in late March, also showed Syrian hamsters to be a good model
for COVID-19-related research. In that study, the hamsters lost weight,
became lethargic, and developed other outward signs of illness.

Kawaoka's group extended this work further, demonstrating that both
low and high doses of the virus, from patient samples collected in the
U.S. and Japan, replicate well in the airways of juvenile hamsters (1
month old) and adults (7 to 8 months old). The virus can also infect
both the upper and lower respiratory tracts.

The research team also showed that SARS-CoV-2 causes severe disease in the lungs of infected animals. This includes lesions and the kind of "ground
glass" appearance often found in lung scans in human patients. Scans also revealed a region of gas in the cavity surrounding the hamster's lungs, indicating severe lung damage. Researchers observed the most severe
effects within eight days after infection, and improvement by 10 days.



========================================================================== "Hamsters infected with SARS-CoV-2 share CT imaging characteristics
with human COVID-19 disease," says Samantha Loeber, a veterinarian and radiologist at UW Veterinary Care.

By day 10 following infection, the researchers no longer detected virus
in the organs of most of the hamsters, but lung damage persisted for 14
days in a majority of the animals, and for at least 20 days in most of
those infected with a high dose.

Overall, the researchers were able to detect virus in all of the
respiratory organs of the infected hamsters within six days of infection,
and also from samples collected from their brains, though these also
contained portions of the olfactory bulb, which is involved in smell and
may have been the source of virus in these samples. The initial dose of
the virus did not affect how much of the virus researchers ultimately
found in the hamster's organs.

The researchers also looked for but did not detect virus in the kidneys,
the small intestine, the colon or in blood.

To determine whether hamsters developed antibodies against SARS-CoV-2
that protected them from reinfection, the researchers administered
another round of the virus to a number of the same animals about three
weeks following initial infection and were unable to detect virus in
their respiratory tracts. They did find virus in the airways of control
animals not previously infected.



==========================================================================
"The animals all possessed antibodies and did not get sick again, which suggests they developed protective immunity," says Pete Halfmann,
a research professor in Kawaoka's U.S. lab. "But we still can't
say how long this protection lasts." In early April, researchers
across the U.S., including at the UW School of Medicine and Public
Health and UW Health, initiated a clinical trial to examine whether
the antibody-bearing component of blood -- the plasma or sera -- from
recovered COVID-19 patients could be given to sick patients to assist in
their recovery. While convalescent plasma has been used in other disease outbreaks, it remains poorly understood as a treatment.

So, Kawaoka's team extracted convalescent sera from previously sick
hamsters and then pooled it together. They infected new hamsters with SARS-CoV-2 and then gave them this antibody-laden sera either one day
or two days following infection.

The hamsters that received treatment within a day of infection had much
lower amounts of infectious virus in their nasal passages and lungs than
those given a mock treatment. Those that received sera on day two showed
a less appreciable benefit, though they still had lower levels of virus
in their respiratory organs compared to control animals.

A study published just last week in Science showed that transfer of
human antibodies to hamsters may also help protect the animals from
severe illness from SARS-CoV-2 infection.

"This shows us that convalescent sera, still experimental in human
patients, may be part of an effective treatment for COVID-19," Kawaoka
adds.

Finally, the research team also obtained the first images of the internal features of the SARS-CoV-2 virus that aid its ability to replicate,
or make copies of itself, in host cells. This, Kawaoka says, warrants
further study.

The study was supported by the Japan Research Program on Emerging and Re- emerging Infectious Diseases, the Japan Project Promoting Support for Drug Discovery, the Japan Initiative for Global Research Network on Infectious Diseases, the Japan Agency for Medical Research and Development Program
for Infectious Diseases Research and Infrastructure, and the U.S. National Institutes of Allergy and Infectious Diseases.


========================================================================== Story Source: Materials provided by
University_of_Wisconsin-Madison. Original written by Kelly April
Tyrrell. Note: Content may be edited for style and length.


========================================================================== Journal References:
1. Masaki Imai, Kiyoko Iwatsuki-Horimoto, Masato Hatta, Samantha
Loeber,
Peter J. Halfmann, Noriko Nakajima, Tokiko Watanabe, Michiko Ujie,
Kenta Takahashi, Mutsumi Ito, Shinya Yamada, Shufang Fan, Shiho
Chiba, Makoto Kuroda, Lizheng Guan, Kosuke Takada, Tammy Armbrust,
Aaron Balogh, Yuri Furusawa, Moe Okuda, Hiroshi Ueki, Atsuhiro
Yasuhara, Yuko Sakai-Tagawa, Tiago J. S. Lopes, Maki Kiso, Seiya
Yamayoshi, Noriko Kinoshita, Norio Ohmagari, Shin-ichiro Hattori,
Makoto Takeda, Hiroaki Mitsuya, Florian Krammer, Tadaki Suzuki,
Yoshihiro Kawaoka. Syrian hamsters as a small animal model for
SARS-CoV-2 infection and countermeasure development.

Proceedings of the National Academy of Sciences, June 22, 2020;
DOI: 10.1073/pnas.2009799117
2. Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler,
Alison Burns,
Wan-ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl,
Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia,
Jonathan Hurtado, Mara Parren, Linghang Peng, Sydney Ramirez,
James Ricketts, Michael J.

Ricciardi, Stephen A. Rawlings, Nicholas C. Wu, Meng Yuan, Davey M.

Smith, David Nemazee, John R. Teijaro, James E. Voss, Ian A. Wilson,
Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G.

Jardine, Dennis R. Burton. Isolation of potent SARS-CoV-2
neutralizing antibodies and protection from disease in a small
animal model. Science, 2020; eabc7520 DOI: 10.1126/science.abc7520 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200622172026.htm

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