PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

Zhang, Z.; Zhou, J.; Ni, P.; Hu, B.; Deng, S.; Xiao, Q.; He, Q.; Li, G.; Xia, Y.; Liu, M.; Wang, C.; Fang, Z.; Xia, N.; Zhang, Z.-R.; Zhang, B.; Cai, K.; Jolicoeur, N.; Xu, Y.; Liu, B.

doi:10.1101/2022.09.26.509414

bioRxiv · 10.1101/2022.09.26.509414

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

Zhang, Z.·Zhou, J.·Ni, P.·Hu, B.·Deng, S.·Xiao, Q.·He, Q.·Li, G.·Xia, Y.·Liu, M.·Wang, C.·Fang, Z.·Xia, N.·Zhang, Z.-R.·Zhang, B.·Cai, K.·Jolicoeur, N.·Xu, Y.·Liu, B.

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Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

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Zhang, Z., Zhou, J., Ni, P., Hu, B., Deng, S., Xiao, Q., He, Q., Li, G., Xia, Y., Liu, M., Wang, C., Fang, Z., Xia, N., Zhang, Z.-R., Zhang, B., Cai, K., Jolicoeur, N., Xu, Y., Liu, B.. 2022-09-26. PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application. https://doi.org/10.1101/2022.09.26.509414

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