Neutralizing Efficacy of Encapsulin Nanoparticles against SARS-CoV2 Variants of Concern
Sara Khaleeq, Nayanika Sengupta, Sahil Kumar, Unnatiben Rajeshbhai Patel, Raju Rajmani, Poorvi Reddy, S. K. Singh Pandey, Randhir Singh, Somnath Dutta, Rajesh P. Ringe, Raghavan Varadarajan
Abstract
Rapid emergence of the SARS-CoV-2 variants has dampened the protective efficacy of existing authorized vaccines. Nanoparticle platforms offer a means to improve vaccine immunogenicity by presenting multiple copies of desired antigens in a repetitive manner which closely mimics natural infection. We have applied nanoparticle display combined with the SpyTag–SpyCatcher system to design encapsulin–mRBD, a nanoparticle vaccine displaying 180 copies of the monomeric SARS-CoV-2 spike receptor-binding domain (RBD). Here we show that encapsulin–mRBD is strongly antigenic and thermotolerant for long durations. After two immunizations, squalene-in-water emulsion (SWE)-adjuvanted encapsulin–mRBD in mice induces potent and comparable neutralizing antibody titers of 105 against wild-type (B.1), alpha, beta, and delta variants of concern. Sera also neutralizes the recent Omicron with appreciable neutralization titers, and significant neutralization is observed even after a single immunization.