Scientific rationale for developing potent RBD-based vaccines targeting COVID-19

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Global COVID-19 vaccination faces supply challenges, necessitating affordable, high-volume vaccine solutions.
• Full-length Spike (S) protein vaccines are available, but demand outstrips supply, particularly for low- and middle-income countries.
• The efficacy of Receptor-Binding Domain (RBD)-based vaccines against emerging SARS-CoV-2 variants remains a key consideration.

Purpose of the Study:

• To review evidence supporting the use of RBD as a sole vaccine immunogen.
• To assess the non-inferiority of RBD-based vaccines compared to full-length S-protein vaccines.
• To evaluate the potential of RBD-based vaccines for broad protection against sarbecoviruses.

Main Methods:

• Review of existing data on humoral and cellular immune responses.
• Comparison of immune responses elicited by RBD-based versus full-length S-protein vaccines.
• Analysis of vaccine efficacy against the prototype SARS-CoV-2 and emerging variants.

Main Results:

• RBD elicits neutralizing antibodies (nAbs), a key biomarker for protection.
• RBD-based vaccines demonstrate high-yielding production potential for affordable, stable doses.
• RBD focuses the immune response on cross-protective determinants, relevant for pan-sarbecovirus vaccine development.

Conclusions:

• RBD is a viable and potentially superior immunogen for COVID-19 vaccines.
• RBD-based vaccines show non-inferiority to full-length S-protein vaccines regarding immune responses.
• RBD holds promise for developing next-generation vaccines against SARS-CoV-2 variants and other sarbecoviruses.