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Review
. 2021 Feb;21(2):73-82.
doi: 10.1038/s41577-020-00480-0. Epub 2020 Dec 18.

Viral targets for vaccines against COVID-19

Lianpan Dai  1 , George F Gao  2
Affiliations
Review

Viral targets for vaccines against COVID-19

Lianpan Dai et al. Nat Rev Immunol. 2021 Feb.

Abstract

Vaccines are urgently needed to control the coronavirus disease 2019 (COVID-19) pandemic and to help the return to pre-pandemic normalcy. A great many vaccine candidates are being developed, several of which have completed late-stage clinical trials and are reporting positive results. In this Progress article, we discuss which viral elements are used in COVID-19 vaccine candidates, why they might act as good targets for the immune system and the implications for protective immunity.

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Conflict of interest statement

L.D. and G.F.G. are listed as inventors on patent applications for a MERS-CoV RBD-dimer vaccine and on pending patent applications for RBD-dimer-based CoV vaccines. The pending patents for RBD-dimers as protein subunit vaccines for MERS-CoV and SARS-CoV-2 have been licensed to Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, China.

Figures

Fig. 1
Fig. 1. Major targets used in COVID-19 vaccine candidates.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains four major structure proteins: spike (S), membrane (M) and envelope (E) proteins, which are embedded on the virion surface, and nucleocapsid (N) protein, which binds viral RNA inside the virion. The S protein trimer in its pre-fusion conformation is shown. The S protein comprises the S1 subunit (which includes the N-terminal domain (NTD) and the receptor-binding domain (RBD)) (the receptor-binding motif (RBM) within the RBD is also labelled) and the S2 subunit (which includes fusion peptide (FP), connecting region (CR), heptad repeat 1 (HR1), heptad repeat (HR2) and central helix (CH)). The SARS-CoV-2 S protein binds to its host receptor, the dimeric human angiotensin-converting enzyme 2 (hACE2), via the RBD and dissociates the S1 subunits. Cleavage at both S1–S2 and S2′ sites allows structural rearrangement of the S2 subunit required for virus–host membrane fusion. The S2-trimer in its post-fusion arrangement is shown. The RBD is an attractive vaccine target. The generation of an RBD-dimer or RBD-trimer has been shown to enhance the immunogenicity of RBD-based vaccines. A stabilized S-trimer shown with a C-terminal trimer-tag is a vaccine target. The pre-fusion S protein is generally metastable during in vitro preparations and prone to transform into its post-fusion conformation. Mutation of two residues (K986 and V987) to proline stabilizes S protein (S-2P) and prevents the pre-fusion to post-fusion structural change.
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