Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2.

Area of Science:

• Vaccinology
• Immunology
• Virology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates improved vaccine strategies.
• Receptor-binding domain (RBD)-only vaccines often lack sustained protective immunity.
• Enhancing antigen processing and immune cell presentation is crucial for effective vaccination.

Purpose of the Study:

• To develop an improved SARS-CoV-2 vaccine by enhancing antigen presentation.
• To evaluate the immunogenicity and protective efficacy of an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F).
• To assess the potential of I-R-F as a single-dose, adjuvant-free vaccine candidate.

Main Methods:

• Engineered an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F).
• Administered a low dose of I-R-F to assess neutralizing antibody (NAb) titers and T cell responses.
• Tested the pan-epitope modified I-R-F (I-P-R-F) vaccine in a rhesus macaque model against a high-dose SARS-CoV-2 challenge.
• Initiated a Phase I/II clinical trial of the human I-P-R-F vaccine (V-01) in healthy adults.

Main Results:

• I-R-F efficiently directs immunity to draining lymph nodes (DLNs).
• A single low dose of I-R-F induced high titers of long-lasting NAbs and comprehensive T cell responses.
• The I-P-R-F vaccine provided rapid and complete protection in rhesus macaques.
• The V-01 vaccine demonstrated safety and elicited strong antiviral immune responses in human trials.

Conclusions:

• The engineered I-R-F vaccine offers potent, long-lasting immunity against SARS-CoV-2.
• I-R-F functions as an effective single-dose, adjuvant-free vaccine.
• The I-P-R-F vaccine (V-01) is a promising next-generation COVID-19 vaccine candidate due to its safety and efficacy.