Viral targets for vaccines against COVID-19

Viral targets for vaccines against COVID-19 - PubMed

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.

PubMed Disclaimer

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. 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.

References

1. Masters S. P. & Perlman S. in Fields virology 6th edn Ch. 28 (eds Knipe, D. M. & Howley, P. M.). 825–858 (Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013).
1. Tizard IR. Vaccination against coronaviruses in domestic animals. Vaccine. 2020;38:5123–5130. - PMC - PubMed
1. Yu J, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020;369:806–811. - PMC - PubMed
1. Mercado NB, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020;586:583–588. - PMC - PubMed
1. Gao Q, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020;369:77–81. - PMC - PubMed