An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Nerea Zabaleta; Wenlong Dai; Urja Bhatt; Cécile Hérate; Pauline Maisonnasse; Jessica A Chichester; Julio Sanmiguel; Reynette Estelien; Kristofer T Michalson; Cheikh Diop; Dawid Maciorowski; Nathalie Dereuddre-Bosquet; Mariangela Cavarelli; Anne-Sophie Gallouët; Thibaut Naninck; Nidhal Kahlaoui; Julien Lemaitre; Wenbin Qi; Elissa Hudspeth; Allison Cucalon; Cecilia D Dyer; M Betina Pampena; James J Knox; Regina C LaRocque; Richelle C Charles; Dan Li; Maya Kim; Abigail Sheridan; Nadia Storm; Rebecca I Johnson; Jared Feldman; Blake M Hauser; Vanessa Contreras; Romain Marlin; Raphaël Ho Tsong Fang; Catherine Chapon; Sylvie van der Werf; Eric Zinn; Aisling Ryan; Dione T Kobayashi; Ruchi Chauhan; Marion McGlynn; Edward T Ryan; Aaron G Schmidt; Brian Price; Anna Honko; Anthony Griffiths; Sam Yaghmour; Robert Hodge; Michael R Betts; Mason W Freeman; James M Wilson; Roger Le Grand; Luk H Vandenberghe

doi:10.1016/j.chom.2021.08.002

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Cell Host Microbe. 2021 Sep 8;29(9):1437-1453.e8. doi: 10.1016/j.chom.2021.08.002. Epub 2021 Aug 7.

Authors

Nerea Zabaleta¹, Wenlong Dai¹, Urja Bhatt¹, Cécile Hérate², Pauline Maisonnasse², Jessica A Chichester³, Julio Sanmiguel¹, Reynette Estelien¹, Kristofer T Michalson³, Cheikh Diop¹, Dawid Maciorowski¹, Nathalie Dereuddre-Bosquet², Mariangela Cavarelli², Anne-Sophie Gallouët², Thibaut Naninck², Nidhal Kahlaoui², Julien Lemaitre², Wenbin Qi⁴, Elissa Hudspeth⁵, Allison Cucalon¹, Cecilia D Dyer³, M Betina Pampena⁶, James J Knox⁷, Regina C LaRocque⁸, Richelle C Charles⁸, Dan Li¹, Maya Kim¹, Abigail Sheridan¹, Nadia Storm⁹, Rebecca I Johnson⁹, Jared Feldman¹⁰, Blake M Hauser¹⁰, Vanessa Contreras², Romain Marlin², Raphaël Ho Tsong Fang², Catherine Chapon², Sylvie van der Werf¹¹, Eric Zinn¹, Aisling Ryan¹, Dione T Kobayashi¹², Ruchi Chauhan¹, Marion McGlynn³, Edward T Ryan¹³, Aaron G Schmidt¹⁴, Brian Price¹⁵, Anna Honko⁹, Anthony Griffiths⁹, Sam Yaghmour⁴, Robert Hodge¹⁶, Michael R Betts⁶, Mason W Freeman¹⁷, James M Wilson³, Roger Le Grand¹⁸, Luk H Vandenberghe¹⁹

Affiliations

¹ Grousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; The Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
² Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
³ Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Novartis Gene Therapies, San Diego, CA, USA.
⁵ Novartis Gene Therapies, NC, USA.
⁶ Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁹ Department of Microbiology and National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁰ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
¹¹ Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, CNRS UMR 3569, Université de Paris, Paris, France; National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.
¹² Translational Innovation Fund, Mass General Brigham Innovation, Cambridge, MA, USA.
¹³ Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
¹⁵ Albamunity, Boston, MA, USA.
¹⁶ Novartis Gene Therapies, Libertyville, IL, USA.
¹⁷ Center for Computational & Integrative Biology, Department of Medicine, and Translational Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁸ Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. Electronic address: roger.le-grand@cea.fr.
¹⁹ Grousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; The Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. Electronic address: luk_vandenberghe@meei.harvard.edu.

Abstract

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.

Keywords: AAV; COVID-19; SARS-CoV-2; adeno-associated virus; durability; immunization; room-temperature stable; single dose; vaccine; viral challenge.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / blood*
Antibodies, Neutralizing / immunology
Antibodies, Viral / blood*
Antibodies, Viral / immunology
COVID-19 / prevention & control*
COVID-19 Vaccines / administration & dosage
COVID-19 Vaccines / genetics
COVID-19 Vaccines / immunology*
Dependovirus / genetics
Dependovirus / metabolism
Female
Humans
Immunogenicity, Vaccine / immunology
Immunologic Memory / immunology
Macaca fascicularis
Macaca mulatta
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / immunology*
T-Lymphocytes / immunology
Transgenes / genetics
Vaccination / methods
Viral Load / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding