Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant

Abstract

The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.

Structure-based dual affinity optimization of a SARS-CoV-1/2 cross-reactive single-domain antibody

“…Animals were euthanized at 5 days post-challenge and viral load was determined for lung tissues by plaque assay. Plaque assay was performed as previously described [ 32 ].…”

Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters

“…The purpose of this study was to first conduct an immunogenicity comparison of the intranasal adjuvant BDX301 using the conventional intramuscular adjuvant aluminum phosphate (AdjuPhos™) as a benchmark in mice with the ancestral Wuhan strain recombinant Spike protein SmT1v3, a FLAG and histidine tag-less version of SmT1, which was previously described elsewhere 25 . In the second part of our study, we assessed the inhibition of virus replication in hamsters immunized with SmT1v3 formulated with BDX301, hereafter referred to as NT-CoV2-1.…”

“…With the persistence of SARS-CoV-2, vaccines based on different technologies and routes of administration warrant investigation. We have previously demonstrated the strong immunogenicity of a resistin-trimerized SARS-CoV-2 Spike antigen, referred to as SmT1 25 . Intramuscular administration of adjuvanted vaccine formulations of SmT1 induced robust immune responses that were strongly protective in a hamster challenge model.…”

Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters

“…The purpose of this study was to first conduct an immunogenicity comparison of the intranasal adjuvant BDX301 using the conventional intramuscular adjuvant aluminum phosphate (AdjuPhos TM ) as a benchmark in mice with the ancestral Wuhan strain recombinant Spike protein SmT1v3, a FLAG and histidine tag-less version of SmT1, which was previously described elsewhere 25 . In the second part of our study, we assessed the inhibition of virus replication in hamsters immunized with SmT1v3 formulated with BDX301, hereafter referred to as NT-CoV2-1.…”

“…Previously, a nasal vaccine comprised of a SARS-CoV-1 recombinant Spike protein with another Proteosome based adjuvant, Protollin, elicited similar serum neutralizing antibody levels as an aluminum hydroxide-adjuvanted formulation containing the same antigen administered intramuscularly, but had significantly lower and undetectable lung SARS-CoV-1 viral titres at administration warrant investigation. We have previously demonstrated the strong immunogenicity of a resistin-trimerized SARS-CoV-2 Spike antigen, referred to as SmT1 25 . Intramuscular administration of adjuvanted vaccine formulations of SmT1 induced robust immune responses that were strongly protective in a hamster challenge model.…”