Figure 1. Structure of SARS-CoV-2. A graphic illustrating the structure of SARS-CoV-2, which shows the viral RNA along with the S, M, E, and N proteins. Figure reprinted from Shaikh et al.4 Licensed under CC BY 4.0. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Figure 2. The SARS-CoV-2 spike protein bound to the ACE2 receptor. (A) The spike protein RBD (light blue, purple) is shown containing the receptor-binding motif (purple) while at the interface of the ACE2 receptor (tan). (B) Interface residues of the RBD (purple) are shown interacting with ACE2 residues in direct contact (red) or extended direct contact (blue) with the RBD. Figure reprinted from Lam et al.6 Licensed under CC BY 4.0. ACE2: angiotensin converting enzyme II; RBD: receptor-binding domain; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Figure 3. Summary of SARS-CoV-2 vaccine types. A summary of several of the major vaccine types being manufactured, including live attenuated (A), inactivated (B, C), viral vector (D), bacterial vector (E), virus-like particles (F), DNA- or RNA-based (G), recombinant protein subunit (H), and synthetic peptides vaccines (I). Figure reprinted from Liu et al.13 Licensed under CC BY 4.0.

Figure 4. Schematic mechanism of manufacturing of viral vector vaccines (A, adenovirus as example) and mRNA vaccines (B). The RNA of SARS-CoV-2 was sequenced, which identified the coding of surface proteins. Using endonuclease methods, an engineered mutated adenovirus vector that carries the SARS-CoV-2 surface protein gene was made. Different from the preparation of adenovirus, the mRNA sequences that encode the spike protein were directly generated. To enhance the stabilities of mRNA and to escape from human immunities, lipid nanoparticles were used to envelope the mRNA. After injection of both viral vector and mRNA vaccines, cells will read the mRNA sequence express the epitope of the surface protein (red within cell) in the cytoplasm or in the nucleus. This will trigger the host’s humoral and cellular immune responses that could potentially contribute to specific immunity to SARS-CoV-2.

Figure 5. Adjuvants improve immunogenicity via different mechanisms. 1. Alum and emulsion such as MF59 generate depots to trap and recruit antigen presenting cells (APCs). 2. By utilizing TLR/NOD agonists, pattern recognition receptors (PRR) were covalently bound to their ligands, followed by the activation of downstream pathways. 3. Aside from APC recruitment, Alum could also induce NLRP3 inflammasome. 4. Depot generation and induction of MHC responses could be obtained by application of MF59 and Freund’s Incomplete Adjuvant (IFA). The image is licensed and authorized by InvivoGen.