Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

Abstract

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

“…The authors observed a weak humoral immune response to 10 μg of trimeric RBD in hamsters, while the titers of specific antibodies in immunized primates were high. When immunized with S-protein, the humoral immune response in both hamsters and primates was equally high [ 29 ]. One more example was published by Dalvey et al The authors obtained virus-like particles (VLPs) containing the engineered RBD variant with increased immunogenicity.…”

“…At the same time, there are no publications that use hamster models to study RBD-based vaccines. The only exception is the preprint by Wu et al, in which the authors observed a weak humoral immune response to RBD in immunized hamsters [ 29 ]. This case and the disturbing lack of hamsters in RBD-based subunit vaccine studies suggests that the predictive value of this animal model may be weak, specifically for vaccines that induce antibodies against RBD.…”