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@ARTICLE{Srivastava2026-mn,
  title     = "Development of a thermostable and broadly neutralizing
               pan-sarbecovirus vaccine candidate",
  author    = "Srivastava, Simran and Kumar, Sahil and Mishra, Suman and
               Rajmani, Raju S and Singh, Randhir and Dutta, Somnath and Ringe,
               Rajesh Prakash and Varadarajan, Raghavan",
  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 na{\"\i}ve 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.",
  journal   = "ACS Infect. Dis.",
  publisher = "American Chemical Society (ACS)",
  volume    =  12,
  number    =  1,
  pages     = "104--118",
  month     =  jan,
  year      =  2026,
  keywords  = "SARS-CoV-2; coronavirus; efficacy; lyophilized; preparedness;
               protein-subunit; thermostability; yield",
  language  = "en"
}