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

• Published in: npj vaccines Vol. 6; no. 1; p. 128
• Main Authors: Kleanthous, Harry, Silverman, Judith Maxwell, Makar, Karen W., Yoon, In-Kyu, Jackson, Nicholas, Vaughn, David W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/699/255; Biomedical and Life Sciences; Biomedicine; Coronaviruses; COVID-19; COVID-19 vaccines; Immune response; Infectious Diseases; Medical Microbiology; Medical research; Pandemics; Proteins; Public Health; Review; Review Article; Severe acute respiratory syndrome coronavirus 2; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-021-00393-6

Vaccination of the global population against COVID-19 is a great scientific, logistical, and moral challenge. Despite the rapid development and authorization of several full-length Spike (S) protein vaccines, the global demand outweighs the current supply and there is a need for safe, potent, high-volume, affordable vaccines that can fill this gap, especially in low- and middle-income countries. Whether SARS-CoV-2 S-protein receptor-binding domain (RBD)-based vaccines could fill this gap has been debated, especially with regards to its suitability to protect against emerging viral variants of concern. Given a predominance for elicitation of neutralizing antibodies (nAbs) that target RBD following natural infection or vaccination, a key biomarker of protection, there is merit for selection of RBD as a sole vaccine immunogen. With its high-yielding production and manufacturing potential, RBD-based vaccines offer an abundance of temperature-stable doses at an affordable cost. In addition, as the RBD preferentially focuses the immune response to potent and recently recognized cross-protective determinants, this domain may be central to the development of future pan-sarbecovirus vaccines. In this study, we review the data supporting the non-inferiority of RBD as a vaccine immunogen compared to full-length S-protein vaccines with respect to humoral and cellular immune responses against both the prototype pandemic SARS-CoV-2 isolate and emerging variants of concern.