A potent, broadly protective vaccine against SARS-CoV-2 variants of concern

Abstract

Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

A Gamma-adapted recombinant subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection

“…This could be related to the notion that K417N/T and E484K substitutions shared by Beta and Gamma viruses simulate a structure that enhances the spectrum of neutralizing activity. In agreement with this hypothesis and our results, a study evaluating the immunogenicity of an S-protein sequence containing these three substitutions in addition to D614G (B.1) demonstrated that the variant vaccine is capable of eliciting high neutralizing Ab titers that cross-reacted with five VOCs in NHP 27 . Moreover, in preclinical and clinical trials Beta derived vaccines induced broadly neutralizing antibodies that can cross-react against different VOC 27,28 in a similar way than the Gamma derived vaccine presented in this work.…”

In-depth characterization of protein N-glycosylation for a COVID-19 variant-design vaccine spike protein

“…Zhongshan Kangtian Shenghe Biotechnology Co., Ltd., QuaCell, one of our partners, obtained the original adherent CHO-K1 cell from Public Health England (PHE) in England. The cells were domesticated in serum-free and suspension culture (protected by patent application) by them, and the cell lines have also been used in previous publications [ 18 , 19 ]. Glu-C and trypsin, both sequencing grade, were purchased from Roche and Sigma-Aldrich, respectively.…”

Efficacy of a stable multivalent broadly protective subunit vaccine platform against SARS-CoV-2 variants of concern

“…Indeed, there is a need to develop broadly protective next-generation SARS-CoV-2 vaccines that will provide better protection against emerging VOCs and further reduce virus shedding and transmission among the vaccinated population. These pan-SARS-CoV-2 VOC vaccine candidates will also inform the development of broadly protective pan-Sarbecovirus and pan-Betacoronavirus vaccine candidates 26 , some of which have been published recently 25,27,28 .…”