An #Alphavirus-derived replicon #RNA #vaccine induces #SARS-CoV-2 neutralizing #antibody and T cell responses in mice and nonhuman primates (Sci Transl Med., abstract)

[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]

An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates

Jesse H. Erasmus1,2, Amit P. Khandhar2,3, Megan A. O’Connor1,4, Alexandra C. Walls5, Emily A. Hemann6,7, Patience Murapa1, Jacob Archer1,3, Shanna Leventhal8, James T. Fuller1, Thomas B. Lewis1,4, Kevin E. Draves1, Samantha Randall1, Kathryn A. Guerriero4, Malcolm S. Duthie2, Darrick Carter2,3,6, Steven G. Reed2,6, David W. Hawman8, Heinz Feldmann8, Michael Gale Jr.4,6,7, David Veesler5, Peter Berglund2 and Deborah Heydenburg Fuller1,4,6,*

1 Department of Microbiology, University of Washington, Seattle, WA 98109, USA. 2 HDT Bio, Seattle, WA 98102, USA. 3 PAI Life Sciences, Seattle, WA 98102, USA. 4 Washington National Primate Research Center, Seattle, WA 98121, USA. 5 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. 6 Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA. 7 Department of Immunology, University of Washington, Seattle, WA 98109, USA. 8 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.

*Corresponding author. Email: fullerdh@uw.edu

Science Translational Medicine  05 Aug 2020: Vol. 12, Issue 555, eabc9396 | DOI: 10.1126/scitranslmed.abc9396

 

A replicating RNA vaccine candidate to fight COVID-19

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is having a major global public health impact necessitating the rapid development of an effective vaccine. Erasmus et al. report that a replicating RNA vaccine stabilized in a lipid inorganic nanoparticle (LION) formulation induced robust antibody responses after a single intramuscular immunization in mice and after a single intramuscular injection at five different sites in macaques. These antibodies neutralized SARS-CoV-2 at titers comparable to those reported in humans convalescing from COVID-19. Prime/boost vaccination of mice and macaques also induced T cell responses that could potentially contribute to protection. This RNA vaccine also induced robust immune responses in aged mice, suggesting the potential for protection in the elderly. These findings support further development of this COVID-19 vaccine candidate.

 

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti–SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

Keywords: SARS-CoV-2; COVID-19; Vaccines.

——

Transient #lymphopenia and interstitial #pneumonia with #endotheliitis in #SARS-CoV-2-infected #macaques (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Transient lymphopenia and interstitial pneumonia with endotheliitis in SARS-CoV-2-infected macaques

Bon-Sang Koo, Hanseul Oh, Green Kim, Eun-Ha Hwang, Hoyin Jung, Youngjeon Lee, Philyong Kang, Jae-Hak Park, Choong-Min Ryu, Jung Joo Hong

The Journal of Infectious Diseases, jiaa486, https://doi.org/10.1093/infdis/jiaa486

Published: 03 August 2020

 

Abstract

Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titres of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.

Macaques, Lymphopenia, Pneumonia, SARS-CoV-2

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: SARS-CoV-2; COVID-19; Animal models.

——-

Small Particle #Aerosol #Exposure of African Green #Monkeys to #MERS-CoV as a #Model for Highly Pathogenic #Coronavirus Infection (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 12—December 2020 | Research

Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

Allison Totura1, Virginia Livingston, Ondraya Frick, David Dyer, Donald Nichols, and Aysegul Nalca

Author affiliations: Author affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA

 

Abstract

Emerging coronaviruses are a global public health threat because of the potential for person-to-person transmission and high mortality rates. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in »35% of cases. Primate models of coronavirus disease are needed to support development of therapeutics, but few models exist that recapitulate severe disease. For initial development of a MERS-CoV primate model, 12 African green monkeys were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose-dependent increase of respiratory disease signs, although all 12 monkeys survived for the 28-day duration of the study. This study describes dose-dependent effects of MERS-CoV infection of primates and uses a route of infection with potential relevance to MERS-CoV transmission. Aerosol exposure of African green monkeys might provide a platform approach for the development of primate models of novel coronavirus diseases.

Keywords: MERS-CoV-2; Coronavirus; Animal models.

——

#Replication-competent #VSV #vaccine vector protects against #SARS-CoV-2-mediated pathogenesis in mice (Cell Host Microbe, abstract)

[Source: Cell Host and Microbe, full page: (LINK). Abstract, edited.]

Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis in mice

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

Published: July 30, 2020 | DOI: https://doi.org/10.1016/j.chom.2020.07.018

 

Highlights

  • A replicating VSV-SARS-CoV-2 vaccine induces high-titer neutralizing antibodies
  • Infectious SARS-CoV-2 is undetectable in the lung of vaccinated mice post-challenge
  • SARS-CoV-2-induced lung inflammation and pathology is decreased in vaccinated mice
  • Transfer of vaccine-derived immune sera to naïve mice protects against SARS-CoV-2

 

SUMMARY

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice expressing human ACE2 and immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naïve mice from SARS-CoV-2 challenge. These data support development of VSV-eGFP-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

Accepted: July 27, 2020 – Received in revised form: July 21, 2020 – Received: July 9, 2020

Publication stage In Press Accepted Manuscript

Lead Contact: Michael S. Diamond, M.D., Ph.D.

Identification DOI: https://doi.org/10.1016/j.chom.2020.07.018

Copyright © 2020 Elsevier Inc.

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

—–

A single #immunization with nucleoside-modified #mRNA #vaccines elicits strong cellular and humoral immune responses against #SARS-CoV-2 in #mice (Immunity, abstract)

[Source: Immunity, full page: (LINK). Abstract, edited.]

A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice

Dorottya Laczkó, Michael J. Hogan, Sushila A. Toulmin, Philip Hicks, Katlyn Lederer, Brian T. Gaudette, Diana Castaño, Fatima Amanat, Hiromi Muramatsu, Thomas H. Oguin III, Amrita Ojha, Lizhou Zhang, Zekun Mu, Robert Parks, Tomaz B. Manzoni, Brianne Roper, Shirin Strohmeier, István Tombácz, Leslee Arwood, Raffael Nachbagauer, Katalin Karikó, Jack Greenhouse, Laurent Pessaint, Maciel Porto, Tammy Putman-Taylor, Amanda Strasbaugh, Tracey-Ann Campbell, Paulo J.C. Lin, Ying K. Tam, Gregory D. Sempowski, Michael Farzan, Hyeryun Choe, Kevin O. Saunders, Barton F. Haynes, Hanne Andersen, Laurence C. Eisenlohr, Drew Weissman, Florian Krammer, Paul Bates, David Allman, Michela Locci, Norbert Pardi

Published: July 30, 2020 | DOI: https://doi.org/10.1016/j.immuni.2020.07.019

 

Highlights

  • mRNA vaccines induce robust type 1 CD4+ and CD8+ T cells in the spleen and lung
  • Vaccine-induced T cells readily exit the vasculature and enter the lung parenchyma
  • mRNA vaccines elicit strong long-lived plasma cell and memory B cell responses
  • mRNA vaccines induce antibodies with potent anti-SARS-CoV-2 neutralization activity

 

Summary

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

Accepted: July 23, 2020 – Received in revised form: July 16, 2020 – Received: June 17, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.immuni.2020.07.019

Copyright Published by Elsevier Inc.

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

——

#Adaptation of #SARS-CoV-2 in #BALB/c #mice for testing #vaccine efficacy (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy

Hongjing Gu1,*, Qi Chen1,*, Guan Yang2,*, Lei He1,*, Hang Fan1,*, Yong-Qiang Deng1,*, Yanxiao Wang2, Yue Teng1, Zhongpeng Zhao1, Yujun Cui1, Yuchang Li1, Xiao-Feng Li1, Jiangfan Li1, Na-Na Zhang1, Xiaolan Yang1, Shaolong Chen1, Yan Guo1, Guangyu Zhao1, Xiliang Wang1, De-Yan Luo1, Hui Wang1, Xiao Yang2, Yan Li3, Gencheng Han3, Yuxian He4, Xiaojun Zhou5, Shusheng Geng6, Xiaoli Sheng6, Shibo Jiang7,†,‡, Shihui Sun1,†,‡, Cheng-Feng Qin1,†,‡, Yusen Zhou1,‡,§ (deceased)

1 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China. 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. 3 Institute of Military Cognition and Brain Sciences, Beijing 100850, China. 4 Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100730, China. 5 Laboratory Animal Center, Academy of Military Medical Sciences, Beijing 100071, China. 6 Beijing JOINN Biologics Co. Ltd, Beijing 100176, China. 7 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

†Corresponding author. Email: shibojiang@fudan.edu.cn (S.J.); sunsh01@163.com (S.S.); qincf@bmi.ac.cn (C.-F.Q.)

* These authors contributed equally to this work.

‡ These authors contributed equally to this work.

§ Deceased.

Science  30 Jul 2020: eabc4730 | DOI: 10.1126/science.abc4730

 

Abstract

The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, we adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young and aged mice following intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: SARS-CoV-2; COVID-19; Animal models.

——

Single-shot Ad26 #vaccine protects against #SARS-CoV-2 in rhesus #macaques (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Noe B. Mercado, Roland Zahn, […] Dan H. Barouch

Nature (2020)

 

Abstract

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in nonhuman primates. Fifty-two rhesus macaques were immunized with Ad26 vectors encoding S variants or sham control and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs following SARS-CoV-2 challenge. Vaccine-elicited neutralizing antibody titres correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in nonhuman primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

——

ChAdOx1 nCoV-19 #vaccine prevents #SARS-CoV-2 pneumonia in rhesus #macaques (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

Neeltje van Doremalen, Teresa Lambe, […] Vincent J. Munster

Nature (2020)

 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was predominantly Th1, as demonstrated by IgG subclass and cytokine expression profiling. Vaccination with ChAdOx1 nCoV-19 (prime-only and prime-boost regimen) induced a balanced Th1/Th2 humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated animals. However, there was no difference in nasal shedding between vaccinated and control animals. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. Safety, immunogenicity and efficacy of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

——

A #vaccine targeting the #RBD of the S protein of #SARS-CoV-2 induces protective #immunity (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity

Jingyun Yang, Wei Wang, […] Xiawei Wei

 

Abstract

The novel Coronavirus SARS-CoV-2 causes a respiratory illness called COVID-19 leading to a pandemic. An effective preventive vaccine against this virus is urgently needed. As the most critical step during infection, SARS-CoV-2 uses its Spike protein receptor-binding domain (S-RBD) to engage with the host cell receptor angiotensin-converting enzyme 2 (ACE2)1,2. Here we showed that a recombinant vaccine comprising residues 319-545 of the S-RBD could induce a potent functional antibody response in the immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after a single dose injection. The sera from the immunized animals blocked RBD binding to ACE2 expressed on the cell surface and neutralized the infection by SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Importantly, the vaccination also provided protection in non-human primates from SARS-CoV-2 challenge in vivo. The elevated RBD-specific antibodies were also found in the sera from patients with COVID-19. Several immune pathways and CD4 T lymphocytes were implicated in the induction of the vaccine antibody response. Our finding highlights the importance of the RBD domain in the SARS-CoV-2 vaccine design and provides the rationale for the development of a protective vaccine through the induction of antibody against the RBD domain.

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

——

#Evaluation of the #mRNA-1273 #Vaccine against #SARS-CoV-2 in Nonhuman #Primates (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Kizzmekia S. Corbett, Ph.D., Barbara Flynn, M.S., Kathryn E. Foulds, Ph.D., Joseph R. Francica, Ph.D., Seyhan Boyoglu-Barnum, Ph.D., Anne P. Werner, B.S., Britta Flach, Ph.D., Sarah O’Connell, M.S., Kevin W. Bock, M.B., Mahnaz Minai, M.S., Bianca M. Nagata, M.S., Hanne Anderson, Ph.D., et al.

 

Abstract

BACKGROUND

Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.

METHODS

Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.

RESULTS

The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.

CONCLUSIONS

Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

Keywords: SARS-CoV-2; COVID-19; Vaccines; Animal models.

——-