Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g. prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S1) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild type signal peptide was best suited for the correct cleavage needed for a natively-folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-γ. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276 ).
Authors 24
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
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Beth Israel Deaconess Medical Center · Harvard University
Affiliation as printed
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Beth Israel Deaconess Medical Center · Harvard University
Affiliation as printed
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
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