Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants

Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particle (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutations. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactive antibodies. ### Competing Interest Statement Jasminka Bozic reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Tanvir Ahmed reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Barthelemy Ontsouka reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Anne-Catherine Fluckiger reports a relationship with VBI Vaccines Inc that includes: consulting or advisory. Abebaw Diress reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Tamara Berthoud reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Xiaoyang Yuan reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Lanjian Yang reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Francisco Diaz-Mitoma reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. David E. Anderson reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. Catalina Soare reports a relationship with VBI Vaccines Inc that includes: employment and equity or stocks. * eVLP : enveloped virus-like particules CoV : coronavirus VOC : Variant of concern VOI : varaint of interest RBD : receptor binding domain NTD : N-terminal domain Ab : antibody nAb : neutralizing antibody MLV : murine leukemia virus ELISA : enzyme-linked-immuno-sorbent-assay PRNT : plaque reduction neutralization test EPT : end-point titer Alum : aluminum phosphate IP : IntraPeritoneal IM : IntraMuscular NRC : National Research Council Canada VIDO : Vaccine and Infectious Disease Organization