The potential of Beta variant containing COVID booster vaccines for chasing Omicron in 2022

Sridhar, Saranya; Chicz, Roman M.; Warren, William H.; Tartaglia, Jim; Savarino, Stephen J.; Gurunathan, Sanjay; Toussaint, Jean‐François

doi:10.1038/s41467-022-33549-6

Cited by 16 publications

(23 citation statements)

References 20 publications

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“…However, E. coli -expressed and mammalian-expressed Beta variant antibodies cross-neutralized Omicron BA.1. This observation aligns with prior reports that infection or vaccination with the Beta variant induces potent, cross-neutralizing antibodies [ 25 , 67 ]. Possibly, the Beta variant RBD expressed in E. coli favorably presents conserved epitopes to the immune system due to the absence of glycosylation.…”

Section: Discussionsupporting

confidence: 92%

Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants

et al. 2022

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The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in E. coli, and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The E. coli-produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in E. coli and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of E. coli as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens.

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Section: Discussionsupporting

confidence: 92%

Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants

et al. 2022

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“…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

Rodríguez²,

Demaría

et al. 2023

Preprint

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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.

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“…These observations have been con rmed in two Phase 3 clinical trials (NCT04762680 and NCT05124171) demonstrating that our Beta-containing booster vaccine candidate delivered a strong immune response against VOCs, including Omicron, in adults primed with mRNA vaccines and conferred strong e cacy against symptomatic infection in adults and participants previously infected with SARS-CoV-2 3,7,8,9 .…”

Section: Introductionmentioning

confidence: 57%

“…An alternative approach could be the selection of a highly immunogenic antigen capable of modulating the immunodominant responses of the parental vaccine while preserving the diversity of the neutralizing responses to target multiple VOCs, including the currently dominant variant. One antigen candidate ful lling these conditions is the Beta variant spike 3 .…”

Section: Introductionmentioning

confidence: 99%

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Beta variant COVID-19 protein booster vaccines elicit durable cross-neutralization against SARS-CoV-2 variants of concern in non-human primates

Pavot

Berry

Kishko

et al. 2022

Preprint

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Rapid spread of the SARS-CoV-2 Omicron subvariants despite the implementation of booster vaccination has raised questions about the durability of protection conferred by current vaccines. Vaccines that can induce broader and more durable immune responses against SARS-CoV-2 post-booster are urgently needed. We recently reported that our Beta-containing protein-based SARS-CoV-2 spike booster vaccine candidates with AS03 adjuvant (CoV2 preS dTM-AS03) elicited robust cross-neutralizing antibody responses up to 3 months in macaques primed with mRNA or protein-based subunit vaccine candidates. Here we demonstrate that the AS03-adjuvanted Beta-containing vaccine formulations induce durable cross-neutralizing antibody responses against Omicron (BA.1) and SARS-CoV-1, and are detectable in all macaques 6 months post-booster. We also describe the induction of consistent and robust memory B cell responses, independent of the levels measured post-primary immunization. These data suggest that a booster dose with a Beta-containing CoV2 preS dTM-AS03 vaccine can induce robust and durable cross-neutralizing responses against a broad spectrum of variants.

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The potential of Beta variant containing COVID booster vaccines for chasing Omicron in 2022

Cited by 16 publications

References 20 publications

Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants

Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants

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

Beta variant COVID-19 protein booster vaccines elicit durable cross-neutralization against SARS-CoV-2 variants of concern in non-human primates

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