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

Bozic, J.; Ahmed, T.; Ontsouka, B.; Fluckiger, A.-C.; Diress, A.; Berthoud, T.; Yuan, X.; Yang, L.; Diaz-Mitoma, F.; Anderson, D. E.; Soare, C.

2021-09-29 immunology
10.1101/2021.09.28.462109 bioRxiv
Show abstract

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.

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