Open AccessTwo-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants
Author(s) -
Linda van Oosten,
Jort J Altenburg,
Cyrielle Fougeroux,
Corinne Geertsema,
Fred van den End,
Wendy Evers,
Adrie H. Westphal,
Simon Lindhoud,
W. van den Berg,
Daan C. Swarts,
Laurens Deurhof,
Andreas Suhrbier,
Thuy T. Le,
Shessy Torres Morales,
Sebenzile K. Myeni,
Marjolein Kikkert,
Adam F. Sander,
Willem A. de Jongh,
Robert Dagil,
Morten A. Nielsen,
Ali Salanti,
Max Søgaard,
Timo M P Keijzer,
Dolf Weijers,
M.H.M. Eppink,
René H. Wijffels,
Monique M. van Oers,
Dirk E. Martens,
Gorben P. Pijlman
Publication year - 2021
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.01813-21
Subject(s) - virology , neutralizing antibody , immunogenicity , virus like particle , vaccination , antibody , biology , viral vector , immunization , virus , recombinant dna , immunology , gene , genetics
Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was ∼11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 μg S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19.