RT Journal Article
SR Electronic
T1 Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.30.227470
DO 10.1101/2020.07.30.227470
A1 Rinke Bos
A1 Lucy Rutten
A1 Joan E.M. van der Lubbe
A1 Mark J.G. Bakkers
A1 Gijs Hardenberg
A1 Frank Wegmann
A1 David Zuijdgeest
A1 Adriaan H. de Wilde
A1 Annemart Koornneef
A1 Annemiek Verwilligen
A1 Danielle van Manen
A1 Ted Kwaks
A1 Ronald Vogels
A1 Tim J. Dalebout
A1 Sebenzile K. Myeni
A1 Marjolein Kikkert
A1 Eric J. Snijder
A1 Zhenfeng Li
A1 Dan H. Barouch
A1 Jort Vellinga
A1 Johannes P.M. Langedijk
A1 Roland C. Zahn
A1 Jerome Custers
A1 Hanneke Schuitemaker
YR 2020
UL http://biorxiv.org/content/early/2020/07/30/2020.07.30.227470.abstract
AB 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).Competing Interest StatementThe authors have declared no competing interest.