Molecular clamp stabilised Spike protein for protection against SARS-CoV-2

Abstract

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution.

Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection

“…COVID-19 vaccine with alum adjuvant demonstrated a Th2-biased response with a low IFN-γ/IL-4 ratio [50], and wse similarly saw a strong Th2 bias of alum for spike protein in the current study. Notably, alum-and squalene-adjuvanted COVID-19 vaccines were both ineffective against nasal virus replication [39]. This contrasts strongly, with the ferret protection data shown here, where Advax-SM adjuvanted rSp, completely prevented both lung and nasal virus replication, an exciting finding as prevention of nasal virus replication could be the key to prevention of virus transmission.…”

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

“…It is evident that the stability of the S glycoprotein is an extremely valuable property for the development of new vaccines against SARS-CoV-2, therefore, improving this property is essential for the development of more stable vaccine candidates. The SARS-CoV-2 vaccine SCB-2019 from Clover pharmaceuticals and SARS-CoV-2 Sclamp from CSL Ltd., share some characteristics with other companies previously mentioned, such as expressing exclusively the ectodomain of the S glycoprotein (80,81), while deleting the signal sequence (SS) of the S glycoprotein. This vaccine uses a platform of subunit protein vaccines (SP) expressed in CHO cells.…”

The COVID-19 Vaccines: Recent Development, Challenges and Prospects

“…Israeli company MigVax is in the process of developing an oral anti-COVID-19 subunit vaccine based on previous research products [ 44 ]. At the same time, The Coalition for Epidemic Preparedness Innovations (CEPI) is working with the University of Queensland to develop a protein vaccine that uses “molecular clamps” to lock the coronavirus protein [ 45 ]. However, the study was terminated due to the potential risk of triggering Human Immunodeficiency Virus-false positives [ 46 ].…”