Immunogenicity of SARS-CoV-2 spike antigens derived from Beta &amp; Delta variants of concern

Akache, Bassel; Renner, Tyler M.; Stuible, Matthew; Rohani, Nazanin; Cepero-Donates, Yuneivy; Deschatelets, Lise; Dudani, Renu; Harrison, Blair A.; Gervais, Christian; Hill, Jonathan D.; Hemraz, Usha D.; Lam, Edmond; Régnier, Sophie; Lenferink, Anne E.G.; Durocher, Yves; McCluskie, Michael J.

doi:10.1038/s41541-022-00540-7

“…A particularly unexpected result of our study is the low immunogenicity of our WU S1-RS09cg vaccine against Wuhan S1, and other VOCs, when compared to Delta and OM S1-RS09cg. Indeed, Delta and Omicron (BA.1) mutations in S have been shown to increase pathogenicity and S fusogenicity, along with increased ACE2 binding to S, when compared to wild-type Wuhan SARS-CoV-2 [ 47 , 52 , 53 , 54 , 55 ]. We hypothesize that this increased ACE2 binding by Delta and Omicron S may explain the increased immunogenicity exhibited by Delta and OM S1-RS09cg when compared to Wuhan S1-RS09cg, however, this will need to be explored further.…”

Section: Discussionmentioning

confidence: 99%

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Khan

¹

,

Kim

²

,

Huang

³

et al. 2023

View full text Add to dashboard Cite

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.

show abstract

“…Most of the variant-adapted vaccines boosters were bivalent or monovalent containing beta and ancestral spike antigens besides Omicron [13][14][15][16] . Interestingly, the Beta variant originated in South Africa, while the Gamma variant originated in Brazil a few months later.…”

Section: Introductionmentioning

confidence: 99%

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

Coria

¹

,

Rodríguez²,

Demaría

³

et al. 2023

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…The copyright holder for this preprint this version posted December 14, 2022. ; https://doi.org/10.1101/2022.12.12.520124 doi: bioRxiv preprint Wuhan SARS-CoV-2 45,[50][51][52][53] . We hypothesize that this increased ACE2 binding by Delta and Omicron S may explain the increased immunogenicity exhibited by Delta and OM S1-RS09cg when compared to Wuhan S1-RS09cg, however, this will need to be explored further.…”

Section: Discussionmentioning

confidence: 99%

“…A particularly unexpected result of our study is the low immunogenicity of our WU S1-RS09cg vaccine against Wuhan S1, and other VOCs, when compared to Delta and OM S1-RS09cg. Indeed, Delta and Omicron (BA.1) mutations in S have been shown to increase pathogenicity and S fusogenicity, along with increased ACE2 binding to S, when compared to wild-type Wuhan SARS-CoV-2 45,[50][51][52][53] . We hypothesize that this increased ACE2 binding by Delta and Omicron S may explain the increased immunogenicity exhibited by Delta and OM S1-RS09cg when compared to Wuhan S1-RS09cg, however, this will need to be explored further.…”

Section: Discussionmentioning

confidence: 99%

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Khan

¹

,

Kim

²

,

Huanga

³

et al. 2022

Preprint

View full text Add to dashboard Cite

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.

show abstract

Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern

Cited by 17 publications

References 29 publications

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

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

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

Contact Info

Product

Resources

About