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

• Published in: Vaccine 2024-08, Vol.42 (20), p.125980, Article 125980
• Main Authors: Garg, Ravendra, Liu, Qiang, Van Kessel, Jill, Asavajaru, Akarin, Uhlemann, Eva-Maria, Joessel, Morgane, Hamonic, Glenn, Khatooni, Zahed, Kroeker, Andrea, Lew, Jocelyne, Scruten, Erin, Pennington, Paul, Deck, William, Prysliak, Tracy, Nickol, Michaela, Apel, Falko, Courant, Thomas, Kelvin, Alyson A., Van Kessel, Andrew, Collin, Nicolas, Gerdts, Volker, Köster, Wolfgang, Falzarano, Darryl, Racine, Trina, Banerjee, Arinjay
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Clinical trials; Combined vaccines; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - immunology; Cricetinae; Disease transmission; Female; Hamsters; Health risks; Humans; Immunogenicity; Laboratories; Manufacturers; Mesocricetus; Proteins; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Squalene; Vaccine development; Vaccine Efficacy; Vaccines; Vaccines, Subunit - immunology; Viral diseases; Viruses
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.05.028

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 model” subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein (the “engine”) linked to a series of flexible receptor binding domains (RBDs; the “cars”) derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant, are immunogenic in Syrian hamsters and subsequently provide protection from infection with SARS-CoV-2 VOCs Omicron (BA.1), 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 13 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.