SARS-CoV-2 Receptor Binding Domain (RBD) Protein-Protein Conjugate Induces Similar or Better Antibody Responses as Spike mRNA in Rhesus Macaques.

Publication date: Jun 17, 2025

Background/Objectives: Rapid development of vaccines against SARS-CoV-2 was pivotal to controlling the COVID-19 pandemic. The emergency also provided a rare opportunity to test novel vaccine platforms such as mRNA in large clinical trials. Most of the early vaccines used SARS-CoV-2 Spike protein as the target antigen. Nevertheless, subsequent studies have shown that Receptor Binding Domain (RBD) of Spike also can yield efficacious vaccines, and we previously demonstrated that chemical conjugation of RBD to a carrier protein, EcoCRM, enhanced antibody responses and induced strong virus neutralization activity in mice. Methods: Here, we compared the immunogenicity of this conjugate to that of an approved mRNA vaccine from Pfizer/BioNTech in rhesus macaques over a period of nine months. Results: AS01-adjuvanted RBD conjugate induced a similar or better antibody response, receptor binding inhibition, and virus neutralization activity against different variants of SARS-CoV-2, compared to mRNA. IgG subclass profiles induced by conjugate and mRNA vaccines were initially dominated by IgG1 and IgG3 then switched to IgG2 and IgG4 dominant profiles during the subsequent six-month period. Polyclonal immune sera from the conjugate and mRNA had similar antibody avidity at multiple time points. Conclusions: In summary, antibody responses in rhesus macaques induced by the RBD-EcoCRM conjugate and the Spike mRNA vaccine are very similar. These results demonstrate the potential for the RBD-EcoCRM conjugate as a vaccine against SARS-CoV-2.

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Concepts Keywords
Biontech protein–protein conjugate
Macaques receptor binding domain
Mice rhesus
Month SARS-CoV-2
Vaccines

Semantics

Type Source Name
disease IDO protein
drug DRUGBANK Tropicamide
disease MESH COVID-19 pandemic
disease MESH emergency
drug DRUGBANK Pinaverium
disease MESH Malaria
pathway KEGG Malaria
disease MESH Allergy
disease MESH Infectious Diseases
disease MESH Viral Diseases
drug DRUGBANK Coenzyme M
disease MESH myocarditis
disease IDO immune response
drug DRUGBANK Clostridium tetani toxoid antigen (formaldehyde inactivated)
disease MESH shingles
disease IDO facility
drug DRUGBANK BIA
drug DRUGBANK Amino acids
drug DRUGBANK L-Cysteine
drug DRUGBANK Aspartame
drug DRUGBANK Carbonate ion
drug DRUGBANK Alkaline Phosphatase
drug DRUGBANK Tromethamine
disease IDO reagent
drug DRUGBANK Proline
disease IDO site
drug DRUGBANK Sodium carbonate
drug DRUGBANK Phosphate ion
disease IDO assay
disease IDO replication
disease IDO cell
disease IDO production
drug DRUGBANK Methylergometrine
disease MESH Dissociation

Original Article

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