Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine

Sonia Jangra, Jana De Vrieze, Angela Choi, Raveen Rathnasinghe, Gabriel Laghlali, Annemiek Uvyn, Simon Van Herck, Lutz Nuhn, Kim Deswarte, Zifu Zhong, Niek Sanders, Stefan Lienenklaus, Sunil David, Shirin Strohmeier, Fatima Amanat, Florian Krammer, Hamida Hammad, Bart N. Lambrecht, Lynda Coughlan, Adolfo García-Sastre, Bruno G. De Geest, Michael Schotsaert
doi: https://doi.org/10.1101/2020.10.23.344085
Sonia Jangra
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jana De Vrieze
2Department of Pharmaceutics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angela Choi
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
3Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raveen Rathnasinghe
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
3Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriel Laghlali
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annemiek Uvyn
2Department of Pharmaceutics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Van Herck
2Department of Pharmaceutics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lutz Nuhn
2Department of Pharmaceutics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kim Deswarte
4Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for inflammation research, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zifu Zhong
5Laboratory for Gene Therapy, Ghent University, Merelbeke, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Niek Sanders
5Laboratory for Gene Therapy, Ghent University, Merelbeke, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan Lienenklaus
6Institute for Laboratory Animal Science, Institute of Immunology, Hannover Medical School, Hannover, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sunil David
7Virovax, Lawrance, KS, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shirin Strohmeier
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
3Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fatima Amanat
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
3Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Florian Krammer
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hamida Hammad
4Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for inflammation research, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bart N. Lambrecht
4Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for inflammation research, Ghent, Belgium
8Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lynda Coughlan
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adolfo García-Sastre
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
9Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
10Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
11The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruno G. De Geest
2Department of Pharmaceutics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Br.DeGeest@ugent.be Michael.Schotsaert@mssm.edu
Michael Schotsaert
1Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, USA
9Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Br.DeGeest@ugent.be Michael.Schotsaert@mssm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The search for vaccines that protect from severe morbidity and mortality as a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Several vaccine candidates are currently being tested in the clinic. Inactivated virus and recombinant protein vaccines can be safe options but may require adjuvants to induce robust immune responses efficiently. In this work we describe the use of a novel amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile). This amphiphile is water soluble and exhibits massive translocation to lymph nodes upon local administration, likely through binding to albumin. IMDQ-PEG-CHOL is used to induce a protective immune response against SARS-CoV-2 after single vaccination with trimeric recombinant SARS-CoV-2 spike protein in the BALB/c mouse model. Inclusion of amphiphilic IMDQ-PEG-CHOL in the SARS-CoV-2 spike vaccine formulation resulted in enhanced immune cell recruitment and activation in the draining lymph node. IMDQ-PEG-CHOL has a better safety profile compared to native soluble IMDQ as the former induces a more localized immune response upon local injection, preventing systemic inflammation. Moreover, IMDQ-PEG-CHOL adjuvanted vaccine induced enhanced ELISA and in vitro microneutralization titers, and a more balanced IgG2a/IgG1 response. To correlate vaccine responses with control of virus replication in vivo, vaccinated mice were challenged with SARS-CoV-2 virus after being sensitized by intranasal adenovirus-mediated expression of the human angiotensin converting enzyme 2 (ACE2) gene. Animals vaccinated with trimeric recombinant spike protein vaccine without adjuvant had lung virus titers comparable to non-vaccinated control mice, whereas animals vaccinated with IMDQ-PEG-CHOL-adjuvanted vaccine controlled viral replication and infectious viruses could not be recovered from their lungs at day 4 post infection. In order to test whether IMDQ-PEG-CHOL could also be used to adjuvant vaccines currently licensed for use in humans, proof of concept was also provided by using the same IMDQ-PEG-CHOL to adjuvant human quadrivalent inactivated influenza virus split vaccine, which resulted in enhanced hemagglutination inhibition titers and a more balanced IgG2a/IgG1 antibody response. Enhanced influenza vaccine responses correlated with better virus control when mice were given a lethal influenza virus challenge. Our results underscore the potential use of IMDQ-PEG-CHOL as an adjuvant to achieve protection after single immunization with recombinant protein and inactivated vaccines against respiratory viruses, such as SARS-CoV-2 and influenza viruses.

Competing Interest Statement

AG-S is inventor in patents on influenza and COVID-19 vaccines owned by the Icahn Shool of Medicine at Mount Sinai. The laboratory of AG-S has research agreements on the study of viral vaccines and prophylaxis with Avimex, Pfizer and 7Hills Pharma. AG-S is a consultant for Avimex and Esperovax

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted October 23, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine
Sonia Jangra, Jana De Vrieze, Angela Choi, Raveen Rathnasinghe, Gabriel Laghlali, Annemiek Uvyn, Simon Van Herck, Lutz Nuhn, Kim Deswarte, Zifu Zhong, Niek Sanders, Stefan Lienenklaus, Sunil David, Shirin Strohmeier, Fatima Amanat, Florian Krammer, Hamida Hammad, Bart N. Lambrecht, Lynda Coughlan, Adolfo García-Sastre, Bruno G. De Geest, Michael Schotsaert
bioRxiv 2020.10.23.344085; doi: https://doi.org/10.1101/2020.10.23.344085
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine
Sonia Jangra, Jana De Vrieze, Angela Choi, Raveen Rathnasinghe, Gabriel Laghlali, Annemiek Uvyn, Simon Van Herck, Lutz Nuhn, Kim Deswarte, Zifu Zhong, Niek Sanders, Stefan Lienenklaus, Sunil David, Shirin Strohmeier, Fatima Amanat, Florian Krammer, Hamida Hammad, Bart N. Lambrecht, Lynda Coughlan, Adolfo García-Sastre, Bruno G. De Geest, Michael Schotsaert
bioRxiv 2020.10.23.344085; doi: https://doi.org/10.1101/2020.10.23.344085

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4122)
  • Biochemistry (8831)
  • Bioengineering (6536)
  • Bioinformatics (23493)
  • Biophysics (11818)
  • Cancer Biology (9235)
  • Cell Biology (13350)
  • Clinical Trials (138)
  • Developmental Biology (7453)
  • Ecology (11432)
  • Epidemiology (2066)
  • Evolutionary Biology (15183)
  • Genetics (10458)
  • Genomics (14057)
  • Immunology (9193)
  • Microbiology (22222)
  • Molecular Biology (8833)
  • Neuroscience (47672)
  • Paleontology (352)
  • Pathology (1432)
  • Pharmacology and Toxicology (2493)
  • Physiology (3741)
  • Plant Biology (8098)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2226)
  • Systems Biology (6046)
  • Zoology (1258)