Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses
npj Vaccines, vol. 5, pp. 91
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 S2) 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
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
-
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
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA
-
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
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
-
Affiliation as printed
Janssen Vaccines & Prevention BV, Leiden, The Netherlands
Cited by 363 stored of 357
Cited by patents worldwide 21 (Lens.org)
-
Lipid nanoparticles for delivering mRNA vaccinesUS12239735B2 2025-03-04 Active
-
CORONAVIRUS VACCINES INDUCING BROAD IMMUNITY AGAINST VARIANTSWO2024209218A1 2024-10-10 Pending
-
新規コロナウイルス組換えスパイクタンパク質、それをコードするポリヌクレオチド、ポリヌクレオチドを含むベクター、およびベクターを含む、コロナウイルス感染を予防または処置するためのワクチンJP2023543387A 2023-10-16 Active
-
Lipid nanoparticles for delivering mRNA vaccinesUS11771652B2 2023-10-03 Active
-
Lipid nanoparticles for delivering mRNA vaccinesUS11771653B2 2023-10-03 Active
-
SARS-COV-2 VACCINESWO2023111725A1 2023-06-22 Pending
-
ANTIGENIC DETERMINANTS, PROTECTIVE IMMUNITY, SERODIAGNOSTIC AND MULTIVALENT SUBUNITS PRECISION VACCINE AGAINST SARS-COV-2WO2023094885A2 2023-06-01 Pending
-
EXPRESSION OF THE SPIKE S GLYCOPROTEIN OF SARS-COV-2 FROM AVIAN PARAMYXOVIRUS TYPE 3 (APMV3)WO2023091988A1 2023-05-25 Pending
-
Compositions and methods for preventing and treating coronavirus infection—SARS-CoV-2 vaccinesUS11498944B2 2022-11-15 Active
-
INTEGRASE DEFECTIVE HIV-BASED LENTIVIRUS MEDIATED NEW GENERATION COVID-19 VACCINE ENCODING SARS-COV-2 SPIKE PROTEINWO2022191801A3 2022-11-03 Pending
-
RECOMBINANT CHIMERIC BOVINE/HUMAN PARAINFLUENZA VIRUS 3 EXPRESSING SARS-COV-2 SPIKE PROTEIN AND ITS USEWO2022232300A1 2022-11-03 Pending
-
MODIFIED CHIMERIC CORONAVIRUS SPIKE PROTEIN FOR ENHANCEMENT OF VIRAL TITERSWO2022200811A1 2022-09-29 Pending
-
ADENOVIRUS TYPE 26 (AD26) VECTOR-BASED VACCINE FOR SARS‑COV‑2, AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOFWO2022193552A1 2022-09-22 Pending
-
NOVEL COMPOSITIONS OF MATTER COMPRISING STABILIZED CORONAVIRUS ANTIGENS AND THEIR USEWO2022178545A1 2022-08-25 Pending
-
SARS-COV-2 IMMUNOGENIC COMPOSITIONS, VACCINES, AND METHODSWO2022167831A1 2022-08-11 Pending
-
AD35 VECTOR VACCINE FOR PREVENTING SARS-COV-2 INFECTIONEP3912638A4 2022-07-13 Discontinued
-
Compositions and methods for preventing and treating coronavirus infection—SARS-CoV-2 vaccinesUS11384122B2 2022-07-12 Inactive
-
KNOCK-IN OF LARGE DNA FOR LONG-TERM HIGH GENOMIC EXPRESSIONWO2022104344A3 2022-06-23 Pending
-
SARS-COV-2 CORONAVIRUS VACCINE AND PREPARATION METHOD THEREFORWO2022077593A1 2022-04-21 Pending
-
SARS-COV-2 IMMUNOGENIC COMPOSITIONS, VACCINES, AND METHODSWO2022013405A1 2022-01-20 Pending