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

Abstract

The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19™). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. Covax-19 vaccine induced high spike protein binding antibody levels that neutralised the original lineage B.1.319 virus from which the vaccine spike protein was derived, as well as the variant B.1.1.7 lineage virus. Covax-19 vaccine also induced a high frequency of spike-specific CD4+ and CD8+ memory T-cells with a dominant Th1 phenotype associated with the ability to kill spike-labelled target cells in vivo . Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus given two weeks after the last immunisation. Notably, ferrets that received the two higher doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting that in addition to lung protection, Covax-19 vaccine may have the potential to reduce virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.

A Spike protein-based subunit SARS-CoV-2 vaccine for pets: safety, immunogenicity, and protective efficacy in juvenile cats

“…The vaccine is prepared from Spike protein ECD with an amino acid sequence corresponding to wild-type SARS-CoV-2 (Wuhan strain) together with some stabilizing mutations that is then codon optimized and expressed in insect cells using the baculovirus transfection system. This spike protein ECD antigen has been previously been shown to be immunogenic, protective, and safe in mice and ferrets in an Australian-developed vaccine called COVAX-19/SpikoGen [30] that has successfully passed phase III clinical trials and in October 2021 received emergency use authorization from the Iranian FDA [24]. This spike protein ECD formulated with an SWE adjuvant (NARUVAX-C19 vaccine) provided complete protection of Syrian hamsters against SARS-CoV-2 infection and prevented transmission to naïve animals placed in the same cage as the challenged animals [22].…”

“…The detailed methodology of obtaining recombinant Spike protein ECD has been described previously [24]. Brie y, the spike protein was identi ed from the SARS-CoV-2 genomic sequence in NCBI (access number: NC 045512) [25].…”

A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines

“…Clinical trials of NVX-CoV2737, which is formulated with the trimeric full-length SARS-CoV-2 S protein and Matrix-M1 adjuvant, have shown that this Matrix-M1-adjuvanted protein vaccine elicits CD4+ T-cell responses biased toward a Th1 phenotype [42,43]. The SARS-CoV-2 S protein formulated with Advax-SM, a combination adjuvant consisting of delta inulin polysaccharide particles (Advax™) and a TLR9-active oligonucleotide-CpG55.2, induced neutralizing antibodies in mice that could neutralize infection by the SARS-CoV-2 wildtype lineage B.1.319 and cross-neutralize the VOC Alpha (B.1.1.7), and protected ferrets against SARS-CoV-2 infection [44].…”

SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants

“…Various generic platforms were used to develop the vaccines, such as using viral protein, Adenovirus-vectored vaccines, using an inactivated virus, mRNA, or RNA-based vaccine [184]. [184], [186][187][188][189][190][191][192][193][194][195][196]. aration, more than 983.1 million vaccine doses have been given worldwide [185].…”

“…Status of COVID-19 Vaccines until 30 November 2021[184],[186][187][188][189][190][191][192][193][194][195][196].…”