What question did this study set out to answer?

To develop a thermostable vaccine candidate targeting multiple sarbecoviruses through enhanced receptor-binding domain derivatives.

January 10, 2026ACS Infectious Diseases0 citationsOpen Access

Development of a Thermostable and Broadly Neutralizing Pan-Sarbecovirus Vaccine Candidate

SSSimran SrivastavaInstitute of Molecular Biology and Biophysics SKSahil KumarCentral Leather Research Institute SMSuman MishraInstitute of Molecular Biology and Biophysics

Key Result

The stabilized RBD cocktail elicited neutralization titers that were enhanced by ∼100-fold in mice compared to unmodified RBDs, indicating potent immunogenicity.

Key Points

To develop a thermostable vaccine candidate targeting multiple sarbecoviruses through enhanced receptor-binding domain derivatives.
Constructed stabilized receptor-binding domain derivatives from multiple sarbecoviruses.
Assessed stabilization effects on yield and thermal stability.
Immunized mice with stabilized RBD cocktail and measured neutralization titers.
Evaluated immunogenicity in naive and preimmunized mice.
Stabilized RBD derivatives improved yield by 3-23-fold.
Significant increase in thermal stability, with resistance to 60 °C incubation.
Immunizations resulted in 100-fold enhancement in neutralization titers.
Vaccine elicited strong neutralizing responses against both homologous and heterologous pseudoviruses.

Structured PICO

Population

Naïve and SARS-CoV-2 preimmunized mice

Intervention

Stabilized and trimerized RBD derivatives of different sarbecoviruses (SARS-CoV-1, WIV-1, RaTG13, RmYN02, BtKY72) as a vaccine formulation

Comparator

Corresponding wild-type (WT) RBDs

Outcome

Neutralization titers against homologous and heterologous pseudoviruses, and protein thermostability/yieldsurrogate

A stabilized, trimerized pan-sarbecovirus RBD vaccine candidate elicits broad neutralizing antibodies without immune imprinting in mice, offering a potential strategy for future sarbecovirus pandemics.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Zoonotic spillover of sarbecoviruses to humans resulted in the SARS-CoV-1 outbreak in 2003 and the current COVID-19 pandemic caused by SARS-CoV-2. In both cases, the viral spike protein (S) is the principal target of neutralizing antibodies that prevent infection. Within the spike, the immunodominant receptor-binding domain (RBD) is the primary target of neutralizing antibodies in COVID-19 convalescent sera and vaccine recipients. We have constructed stabilized RBD derivatives of different sarbecoviruses: SARS-CoV-1 (Clade 1a), WIV-1 (Clade 1a), RaTG13 (Clade 1b), RmYN02 (Clade 2), and BtKY72 (Clade 3). Stabilization enhanced yield by 3-23-fold. The RBD derivatives were conformationally intact, as assayed by binding to multiple broadly neutralizing antibodies. The stabilized RBDs show significant enhancement in apparent Tm, exhibit resistance to a 2-h incubation at temperatures up to 60 °C in PBS in contrast to the corresponding WT RBDs, and show prolonged stability of over 15 days at 37 °C after lyophilization. In mice immunizations, both stabilization and trimerization significantly enhanced elicited neutralization titers by ∼100-fold. The stabilized RBD cocktail elicited highly neutralizing titers against both homologous and heterologous pseudoviruses. The immunogenicity of the vaccine formulation was assessed in both naïve and SARS-CoV-2 preimmunized mice, revealing an absence of immune imprinting, thus indicating its suitability for use in future sarbecovirus-origin epidemics or pandemics.

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