S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

Abstract

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

Viral targets for vaccines against COVID-19

“…Vaccination of the S-trimer together with AS03 (a squalene-based adjuvant developed by GlaxoSmithKline) or CpG 1018 (a Toll-like receptor 9 agonist adjuvant developed by Dynavax) elicited high levels of nAbs and T H 1 cell-biased responses in mice and NHPs. It could protect NHPs from challenge with SARS-CoV-2, with reduced viral loads and pathology in the lungs 84 . This candidate vaccine is currently under evaluation in phase I clinical trials ( TaBle 1).…”

CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

“…The vast majority of COVID-19 vaccines use the full length or the receptor binding domain of spike (S) protein on the surface of the virus as the antigen, as this binds to human angiotensin converting enzyme 2 (hACE2) for cellular entry and is the major neutralizing antibody inducing antigen [5]. Various modifications including modification of two prolines and inactivation of the furin site have been made to the S protein to lock in its prefusion form to enhance its stability and immunogenicity, and this has been applied to current vaccine development [6][7][8][9]. We have previously reported preclinical immunogenicity and safety results of prefusion stabilized S protein, S-2P, adjuvanted with CpG 1018 and aluminum hydroxide (alum) in rodent models [10].…”

Recombinant protein vaccines, a proven approach against coronavirus pandemics

“…A recombinantly produced homotrimer of the full-length S-protein also serves as the antigen in Clover Biopharmaceuticals’ S-Trimer vaccine [ 11 ]. Using the company’s Trimer-tag platform, originally developed for cancer therapeutics, Clover has genetically fused the SARS-COV-2 S-protein (aa residues 1-1211) to human C-propeptide of alpha1(I) collagen.…”

“…The immunostimulatory effects of CpG are optimized by keeping the oligonucleotide and the vaccine antigen in close proximity. Driven by electrostatic interaction, CpG 1018 binds well to aluminum hydroxide and is therefore well-suited for co-formulation with aluminum-based subunit vaccines [ 11 ].…”

“…In the study, 30 μg of the S-trimer adjuvanted with either AS03 or CpG1018/alum were used to immunize Rhesus macaques on Day 0 and Day 21. On day 35, neutralizing antibody titers in the AS03-adjuvanted S-Trimer group (IC50 = 20,234) were significantly higher than CpG 1018 plus alum group (IC50 = 11,682), however, the lymphocyte response seems to sustain in the CpG 1018 plus alum group longer [ 11 ]. Clover biopharmaceuticals have partnered with GlaxoSmithKline to produce the vaccine for the current Phase 1 study [ 156 ] and have formed an advisory board for global vaccine development and access [ 157 ].…”