A SARS-CoV-2 Wuhan spike virosome vaccine induces superior neutralization breadth compared to one using the Beta spike

Yme U Van Der Velden,Khadija Tejjani,Ronald Kempers,Melissa Oomen,Esther Siteur-Van Rijnstra,Meliawati Poniman,Tom G Caniels,Marloes Grobben,Marit J Van Gils,Judith A Burger,Rogier W Sanders,Toon Stegmann,Denise Guerra

doi:10.1038/s41598-022-07590-w

Yme U Van Der Velden, Khadija Tejjani + Show 11 more

Open Access

https://doi.org/10.1038/s41598-022-07590-w

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Abstract

Current SARS-CoV-2 vaccines are effective, but long-term protection is threatened by the emergence of virus variants. We generated a virosome vaccine containing the Beta spike protein and compared its immunogenicity in mice to a virosome vaccine containing the original Wuhan spike. Two administrations of the virosomes induced potent SARS-CoV-2 neutralizing antibodies in both vaccine groups. The level of autologous neutralization in Beta-vaccinated mice was similar to the level of autologous neutralization in Wuhan-vaccinated mice. However, heterologous neutralization to the Wuhan strain in Beta-vaccinated mice was 4.7-fold lower than autologous neutralization, whereas heterologous neutralization to the Beta strain in Wuhan-vaccinated mice was reduced by only 1.9-fold compared to autologous neutralization levels. In addition, neutralizing activity against the D614G, Alpha and Delta variants was also significantly lower after Beta spike vaccination than after Wuhan spike vaccination. Our results show that Beta spike vaccination induces inferior neutralization breadth. These results are informative for programs aimed to develop broadly active SARS-CoV-2 vaccines.

Highlights

Current SARS-CoV-2 vaccines are effective, but long-term protection is threatened by the emergence of virus variants
While a number of effective vaccines have been approved and are being rolled out, the continuous emergence of new genetic and antigenic SARS-CoV-2 virus variants poses a threat to the long-term effectiveness of these vaccines
The vast majority of SARS-CoV-2 vaccines are based on the spike (S) glycoprotein, a homotrimeric glycoprotein that plays a pivotal role in viral entry and consists of an S1 subunit including the receptor binding domain (RBD) and an S2 subunit containing the fusion p eptide[28, 29]

Summary

Introduction

Current SARS-CoV-2 vaccines are effective, but long-term protection is threatened by the emergence of virus variants. We generated virosome vaccines using the SARS-CoV-2 Beta and original Wuhan spike proteins as immunogens. None of the mice harbored SARS-CoV-2-specific binding and/or neutralizing antibodies before vaccination (Fig. S1A + B).

Results

Conclusion