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

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.