Efficacy of a stable multivalent broadly protective subunit vaccine platform against SARS-CoV-2 variants of concern

Abstract

Abstract The emergence and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for rapid vaccine development platforms that can be updated to counteract emerging variants of currently circulating and future emerging coronaviruses. Here we report the development of a “train engine and car” subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein linked to a series of flexible receptor binding domains (RBDs) derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with the SWE adjuvant are immunogenic in Syrian hamsters and subsequently provide protection from challenge with SARS-CoV-2 VOCs Omicron, Delta, and Beta. Importantly, the bivalent and trivalent vaccine candidates offered protection against some heterologous SARS-CoV-2 VOCs that were not included in the vaccine design, demonstrating the potential for broad protection against a range of different VOCs. Furthermore, these formulated vaccine candidates were stable at 2–8 °C for up to 12 months post-formulation, highlighting their utility in low-resource settings. Indeed, our vaccine platform will enable the development of safe and broadly protective vaccines against emerging betacoronaviruses that pose a significant health risk for humans and agricultural animals.