Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models

Autor: Hugo Mouquet, Benjamin Vesin, Houda Tabbal, Françoise Guinet, Jodie Lopez, Pierre Authié, Laurence Fiette, Marine Le Dudal, Catherine Blanc, François Anna, Maryline Bourgine, Nicolas Escriou, David Hardy, Fanny Moncoq, Kirill Nemirov, Fabien Nevo, Annette Martin, Pierre Charneau, Philippe Souque, Laleh Majlessi, Emeline Simon, Amandine Noirat, Min Wen Ku
Přispěvatelé: Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys, Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Mutualiste de Montsouris (IMM), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, The authors are grateful to Prof. Sylvie van der Werf (National Reference Centre for Respiratory Viruses, Institut Pasteur, France) for providing the BetaCoV/France/IDF0372/2020 SARS-CoV-2 clinical isolate, supplied through the European Virus Archive Global (Evag), funded by the European Union’s Horizon 2020 program under grant agreement no. 653316. This work was also supported by grants from Institut Pasteur, TheraVectys, and Agence Nationale de la Recherche HuMoCID. M.W.K. is part of the Pasteur - Paris University PhD program and received funding from Institut Carnot Pasteur Microbes & Santé and the European Union’s Horizon 2020 program under Marie Sklodowska-Curie grant agreement no. 665807., ANR-20-COVI-0028,HuMoCID,Développement de modèles murins de COVID-19(2020), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris]-TheraVectys, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hardy, David, Développement de modèles murins de COVID-19 - - HuMoCID2020 - ANR-20-COVI-0028 - COVID-19 - VALID, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
[SDV]Life Sciences [q-bio]
Respiratory System
lentiviral vectors
immunoglobulin A
Antibodies
Viral
Mice
Transduction (genetics)
0302 clinical medicine
Cricetinae
respiratory tracts
0303 health sciences
Viral Load
3. Good health
Vaccination
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
in vivo Ad5 transduction
Models
Animal
Spike Glycoprotein
Coronavirus
Lentivirus
Female
COVID-19 Vaccines
Genetic Vectors
Immunization
Secondary
Biology
Microbiology
Article
Viral vector
03 medical and health sciences
Immune system
[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology
Virology
boost-target
medicine
Animals
neutralizing antibodies
Immunity
Mucosal
Administration
Intranasal
030304 developmental biology
SARS-CoV-2
lung inflammation
COVID-19
beta-coronavirus
Vaccine efficacy
biology.organism_classification
Antibodies
Neutralizing
intranasal vaccination
Immunology
mucosal immunity
Parasitology
Nasal administration
golden hamsters
[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
030217 neurology & neurosurgery
Respiratory tract
Zdroj: Cell Host & Microbe
Cell Host & Microbe, 2020, ⟨10.1016/j.chom.2020.12.010⟩
ISSN: 1931-3128
DOI: 10.1016/j.chom.2020.12.010⟩
Popis: To develop a vaccine candidate against COVID-19, we generated a Lentiviral Vector (LV), eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, confers only partial protection, despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in > 3 log10 decrease in the lung viral loads and reduces local inflammation. Moreover, both integrative and non-integrative LV platforms display strong vaccine efficacy and inhibit lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and closely mirror human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of the LV-based vaccination against SARS-CoV-2 and designate intranasal immunization as a powerful approach against COVID-19.
Graphical Abstract
Highlights A lentiviral vector encoding for Spike shows preclinical efficacy as a COVID-19 vaccine. Targeting the immune response to the upper respiratory tract provides critical protection. Intranasal vaccination induces protective mucosal immunity against SARS-CoV-2 in rodents. Lung anti-Spike IgA responses correlate with protection and reduced inflammation.
Ku and colleagues present a lentiviral vaccination vector that encodes a full-length, membrane anchored form of SARS-CoV-2 Spike glycoprotein that induces neutralizing antibodies and T-cell responses. An intranasal boost strategy triggers a localized immune response in the upper respiratory tract that provides disease protection in mouse and hamster COVID-19 models.
Databáze: OpenAIRE
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