A Gamma-adapted recombinant subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.

Abstract

The COVID-19 pandemic continues with the emergence of successive new variants of concern (VOC). One strategy to prevent breakthrough infections is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD recombinant vaccine candidate derived from the Gamma SARS-CoV-2 variant adjuvanted with alum. Gamma RBD-derived antigen elicited better neutralizing antibody and T cell responses than formulation containing ancestral RBD antigen. The Gamma-adapted subunit vaccine elicited a long-lasting antibody response with cross-neutralizing activity against different VOC including the Omicron variant. Additionally, Gamma variant RBD-adapted vaccine elicited robust T cells responses with induction of Th1 and CD8+ T cell responses in spleen and lung. Vaccine-induced immunity protected K18-hACE2 mice from intranasal challenge with SARS-CoV-2 increasing survival, reducing body weight loss and viral burden in the lungs and brain. Importantly, the subunit vaccine demonstrated a potent effect as heterologous booster of different vaccine platforms including the non-replicating adenovirus vaccine ChAdOx1-S, the mRNA vaccine BNT162b2 and the inactivated SARS-CoV-2 vaccine BBIBP-CorV, increasing cross-reactive antibody responses. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate to combat SARS-CoV-2 variants including Omicron.