Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward

Figures & data

Figure 1. Schematic illustration of SARS-CoV-2 virus structure with its major proteins (a), spike protein trimer (b) with receptor-binding domain (c)

The four structural proteins, the spike glycoprotein (S), the membrane glycoprotein (M), the nucleocapsid protein (N), and the envelope protein (E). The ‘S’ glycoprotein consists of homotrimers that protrudes from the viral surface. The ‘receptor binding domain’ (RBD) specifically recognizes human angiotensin-converting enzyme 2 (hACE2) as its receptor and uses it to enter cells.

Table 1. Landscape of SARS-CoV-2 candidate vaccines: Vaccine platform, their attributes, and status of development (References:^{2,3,16,79,81,82})

Vaccine platform	Vaccine candidates under clinical trials*	Safety	Speed of development	Global distribution and scalability	NAb production	T-cell immune responses	Advantage	Disadvantage	Existing example/Same platform for non-HCoV candidates
Inactivated	Seven	Some concerns	Medium	Feasible	Moderate	Probably lower	-Traditional & easy to develop -Preserve virus particle structure -Can be formulated with various adjuvants	-Possible hypersensitivity -Th-2 bias? -Possible ADE?	SARS
Live attenuated	None	Significant concerns	Slow	Feasible	Probably high	Probably good	-Highly immunogenic -Good cellular responses -Can be given intranasally that can induce mucosal immunity too	-Substantial safety concerns (Reversion to virulent strain) -Cold chain requirement, -Risk to immunocompromised	Several (OPV, MMR, Varicella, Influenza, etc)
Non-Replicating Viral Vector	Nine	High	Medium	Feasible	Moderate	Probably good	-Despite a live virus vaccine, safety not an issue, -should elicit better immune responses than killed/subunit vaccines -Good cellular responses	-Selection of safe vector-a must. -Immune response to vector may render vaccine less effective	Ebola, MERS, influenza, TB, Chikungunya, Zika, MenB, plague
Replicating Viral Vector	Three	Some concerns	Medium	Feasible	Probably good	Good	-Mimic natural infection “dose sparing effect” (less dose required as compared to non-replicating viral vector vaccine-Often induce innate immune response too -Some vectors may be given intranasally and induce mucosal immunity	Selection of safe vector-a must. -Immune response to vector may render vaccine less effective	HIV
RNA	Six	High	Fast	May be difficult	Moderate	Probably good	-Rapid development. -Easy to make	- No approved RNA vaccines -Unlikely to induce mucosal immunity -Required frozen storage: big challenge in developing and underdeveloped countries	multiple candidates in the pipeline
DNA	Four	High	Fast	Some concerns	Moderate	Probably good	Rapid development; Easy to make	-Low immunogenicity -Approved for veterinary cases; -No approved vaccines for use in humans	None (multiple candidates in the pipeline)
Protein Subunit	Thirteen	High	Slow	Feasible	High	Probably lower	-High safety profile -Consistent production -High NAbs production	-Need appropriate adjuvant, -Cost-effectiveness may vary	RSV, CCHF, HPV, VZV, Influenza, Ebola
VLP	Two	High	Slow	Feasible	High	Probably lower	-Multimeric antigen display -Preserve virus particle structure	-Require optimum assembly condition	Flu, Rotavirus, Norovirus, West Nile virus, Cancer, HPV

* For a complete list of vaccine candidates in Clinical Trials and preclinical stages, visit: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines VLP: vaccine-like particle

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