Investigational COVID-19 vaccine candidate prevents severe clinical
disease in animals
Research team reports vaccine protection against severe COVID-19-related pneumonia and death

Date:
September 3, 2020
Source:
Beth Israel Deaconess Medical Center
Summary:
New research demonstrates that a candidate COVID-19 vaccine
elicited robust immune response in Syrian golden hamsters and
prevented severe clinical disease -- including weight loss,
pneumonia and death.



FULL STORY ==========================================================================
Most people with COVID-19 have relatively mild disease, but a subset
of people develop severe pneumonia and respiratory failure, potentially
leading to death.

Beth Israel Deaconess Medical Center (BIDMC) immunologist Dan H. Barouch,
MD, PhD, and colleagues showed in recently published previous work that a candidate COVID-19 vaccine raised neutralizing antibodies that robustly protected non- human primates (NHPs) against SARS-CoV-2, the virus that
causes COVID-19. Now, in new research published today in Nature Medicine, Barouch and colleagues demonstrated that the optimal vaccine elicited
robust immune response in Syrian golden hamsters and prevented severe
clinical disease -- including weight loss, pneumonia and death.


==========================================================================
"We recently reported that an Ad26-based SARS-CoV-2 vaccine provided
robust protection in rhesus macaques, and this vaccine is currently being evaluated in humans," said Barouch, who is Director of BIDMC's Center
for Virology and Vaccine Research. "However, nonhuman primates typically
don't get severe clinical disease, and thus it was important to study
whether this vaccine could prevent severe pneumonia and death due to
SARS-CoV-2 in hamsters, which are more susceptible to clinical disease."
The vaccine -- developed through a collaboration between BIDMC and Johnson
& Johnson (J&J) -- uses a common cold virus, called adenovirus serotype 26 (Ad26), to deliver the SARS-CoV-2 spike protein into host cells, where
it stimulates the body to raise immune responses against the coronavirus.

Barouch's group and J&J developed a series of vaccine candidates designed
to express different variants of the SARS-CoV-2 spike protein, which is
the major target for neutralizing antibodies.

In the current study, the researchers immunized Syrian golden hamsters
with a single injection of the Ad26-based SARS-CoV-2 vaccine, which
induced neutralizing antibodies in all animals. Four weeks later, the
animals were exposed to a high dose of SARS-CoV-2. Vaccinated animals
lost less weight and had less virus in their lungs and other organs than unvaccinated control animals. Vaccinated animals also demonstrated lower mortality. Moreover, the researchers found that neutralizing antibody
responses were inversely correlated with weight loss and viral loads in respiratory tissues. The Ad26.COV2.S vaccine is currently being evaluated
in clinical studies to establish the performance of the vaccine candidate
in humans.

"This hamster model of severe COVID-19 disease should prove useful to complement current nonhuman primate models in the evaluation of candidate vaccines and therapeutics," said Barouch, who is also the William Bosworth Castle Professor of Medicine at Harvard Medical School, a member of the
Ragon Institute of MGH, MIT, and Harvard, and the co-leader of the vaccine working group of the Massachusetts Consortium on Pathogen Readiness.

In July 2020, investigators at BIDMC and other institutions initiated
a first- in-human Phase 1/2 clinical trial of the Ad26.COV2.S vaccine
in healthy volunteers. Kathryn E. Stephenson, MD, MPH, is the principal investigator for the trial at BIDMC, which is funded by Janssen Vaccines & Prevention, B.V., a pharmaceutical research arm of Johnson & Johnson.

Pending clinical trial outcomes, the Ad26.COV2.S vaccine is on track
to start a phase 3 efficacy trial in up to 60,000 participants in
September 2020.

Co-authors included Lisa H. Tostanoski, Katherine McMahan, Noe D. Mercado, Jingyou Yu, Cesar Piedra-Mora, Esther A. Bondzie, Gabriel Dagotto, Make S.

Gebre, Catherine Jacob-Dolan, Fijian Lin, Shant H. Mahrokian, Felix
Nampanya, and Ramya Nityanandam of BIDMC; Frank Wegman, Jerome Custers,
Hanneke Schiutemaker, and Roland Zahn of Janssen Vaccines & Prevention
BV; Amanda J.

Martinot, Linda M. Wrijil, and Sarah Ducat of Cummings School of
Veterinary Medicine at Tufts University; Carolin Loos, Caroline Atyeo, Stephanie Fischinger, John S. Burke, Jared Feldman, Blake M. Hauser,
Timothy M.

Caradonna, Galit Alter, and Aaron G. Schmidt of Ragon Institute of MGH,
MIT, and Harvard; Chi N. Chan, Stephen Bondoc, Carly E. Starke, Michael Nekorchuck, Kathleen Busman-Sahay, Jacob D. Estes of Oregon Health &
Sciences University; Laurent Pessaint, Maciel Porto, Vanessa Ali, Dalia Benetiene, Komlan Tevi, Hanne Andersen, and Mark G. Lewis of Bioqual;
and Douglas A. Lauffenburger of Massachusetts Institute of Technology.

Barouch, Wegman, Custers, Schuitemaker, and Zahn are co-inventors on
related vaccine patents. Wegman, Custers, Schuitemaker, and Zahn are
employees of Janssen Vaccines & Prevention BV and hold stock in Johnson
& Johnson.

This project was funded in part by the Bill & Melinda Gates Foundation
(INV- 226 006131); Janssen Vac-cines & Prevention BV; Ragon Institute of
MGH, MIT, and Harvard; Mark and Lisa Schwartz Foundation; Massachusetts Consortium on Pathogen Readiness (MassCPR); the National Institutes
of Health (OD024917, AI129797, AI124377, AI128751, AI126603 to D.H.B.;
AI007387 to L.H.T.; AI146779 to A.G.S.; AI135098 to A.J.M.; and OD011092, OD025002 to J.D.E.); the Department of Health and Human Services
Biomedical Advanced Research and Development Authority (BARDA) under
contract HHS0100201700018C; a Fast Grant, Emergent Ventures, Mercatus
Center at George Mason University to A.J.M.


========================================================================== Story Source: Materials provided by
Beth_Israel_Deaconess_Medical_Center. Original written by Lindsey Diaz-MacInnis. Note: Content may be edited for style and length.


========================================================================== Journal References:
1. Lisa H. Tostanoski, Frank Wegmann, Amanda J. Martinot, Carolin Loos,
Katherine McMahan, Noe B. Mercado, Jingyou Yu, Chi N. Chan, Stephen
Bondoc, Carly E. Starke, Michael Nekorchuk, Kathleen Busman-Sahay,
Cesar Piedra-Mora, Linda M. Wrijil, Sarah Ducat, Jerome Custers,
Caroline Atyeo, Stephanie Fischinger, John S. Burke, Jared Feldman,
Blake M.

Hauser, Timothy M. Caradonna, Esther A. Bondzie, Gabriel
Dagotto, Makda S. Gebre, Catherine Jacob-Dolan, Zijin Lin, Shant
H. Mahrokhian, Felix Nampanya, Ramya Nityanandam, Laurent Pessaint,
Maciel Porto, Vaneesha Ali, Dalia Benetiene, Komlan Tevi, Hanne
Andersen, Mark G. Lewis, Aaron G. Schmidt, Douglas A. Lauffenburger,
Galit Alter, Jacob D. Estes, Hanneke Schuitemaker, Roland Zahn,
Dan H. Barouch. Ad26 vaccine protects against SARS-CoV-2 severe
clinical disease in hamsters. Nature Medicine, 2020; DOI:
10.1038/s41591-020-1070-6
2. Noe B. Mercado, Roland Zahn, Frank Wegmann, Carolin Loos, Abishek
Chandrashekar, Jingyou Yu, Jinyan Liu, Lauren Peter, Katherine
McMahan, Lisa H. Tostanoski, Xuan He, David R. Martinez, Lucy
Rutten, Rinke Bos, Danielle van Manen, Jort Vellinga, Jerome
Custers, Johannes P. Langedijk, Ted Kwaks, Mark J. G. Bakkers,
David Zuijdgeest, Sietske K. Rosendahl Huber, Caroline Atyeo,
Stephanie Fischinger, John S. Burke, Jared Feldman, Blake M. Hauser,
Timothy M. Caradonna, Esther A. Bondzie, Gabriel Dagotto, Makda
S. Gebre, Emily Hoffman, Catherine Jacob-Dolan, Marinela Kirilova,
Zhenfeng Li, Zijin Lin, Shant H. Mahrokhian, Lori F.

Maxfield, Felix Nampanya, Ramya Nityanandam, Joseph P. Nkolola,
Shivani Patel, John D. Ventura, Kaylee Verrington, Huahua Wan,
Laurent Pessaint, Alex Van Ry, Kelvin Blade, Amanda Strasbaugh,
Mehtap Cabus, Renita Brown, Anthony Cook, Serge Zouantchangadou,
Elyse Teow, Hanne Andersen, Mark G.

Lewis, Yongfei Cai, Bing Chen, Aaron G. Schmidt, R. Keith Reeves,
Ralph S. Baric, Douglas A. Lauffenburger, Galit Alter, Paul
Stoffels, Mathai Mammen, Johan Van Hoof, Hanneke Schuitemaker, Dan
H. Barouch. Single-shot Ad26 vaccine protects against SARS-CoV-2
in rhesus macaques. Nature, 2020; DOI: 10.1038/s41586-020-2607-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200903121956.htm

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