TY - JOUR

T1 - Two-component nanoparticle vaccine displaying glycosylated spike S1 domain induces neutralizing antibody response against SARS-CoV-2 variants

AU - van Oosten, Linda

AU - Altenburg, Jort J

AU - Fougeroux, Cyrielle

AU - Geertsema, Corinne

AU - van den End, Fred

AU - Evers, Wendy A C

AU - Westphal, Adrie H

AU - Lindhoud, Simon

AU - van den Berg, Willy

AU - Swarts, Daan C

AU - Deurhof, Laurens

AU - Suhrbier, Andreas

AU - Le, Thuy T

AU - Torres Morales, Shessy

AU - Myeni, Sebenzile K

AU - Kikkert, Marjolein

AU - Sander, Adam F

AU - de Jongh, Willem Adriaan

AU - Dagil, Robert

AU - Nielsen, Morten A

AU - Salanti, Ali

AU - Søgaard, Max

AU - Keijzer, Timo M P

AU - Weijers, Dolf

AU - Eppink, Michel H M

AU - Wijffels, René H

AU - van Oers, Monique M

AU - Martens, Dirk E

AU - Pijlman, Gorben P

PY - 2021/10/26

Y1 - 2021/10/26

N2 - 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. IMPORTANCE Vaccination is essential to reduce disease severity and limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protein-based vaccines are useful to vaccinate the world population and to boost immunity against emerging variants. Their safety profiles, production costs, and vaccine storage temperatures are advantageous compared to mRNA and adenovirus vector vaccines. Here, we use the versatile and scalable baculovirus expression vector system to generate a two-component nanoparticle vaccine to induce potent neutralizing antibody responses against SARS-CoV-2 variants. These nanoparticle vaccines can be quickly adapted as boosters by simply updating the antigen component.

AB - 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. IMPORTANCE Vaccination is essential to reduce disease severity and limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protein-based vaccines are useful to vaccinate the world population and to boost immunity against emerging variants. Their safety profiles, production costs, and vaccine storage temperatures are advantageous compared to mRNA and adenovirus vector vaccines. Here, we use the versatile and scalable baculovirus expression vector system to generate a two-component nanoparticle vaccine to induce potent neutralizing antibody responses against SARS-CoV-2 variants. These nanoparticle vaccines can be quickly adapted as boosters by simply updating the antigen component.

U2 - 10.1128/mBio.01813-21

DO - 10.1128/mBio.01813-21

M3 - Journal article

C2 - 34634927

VL - 12

JO - mBio

JF - mBio

SN - 2161-2129

IS - 5

M1 - e0181321

ER -