Comparison of Immune Response between SARS, MERS, and COVID-19 Infection, Perspective on Vaccine Design and Development

Table 1

Potential vaccine candidates developed for SARS-CoV and MERS-CoV.

Vaccine platform	Immunogen	Animal model	Route of injection	Adjuvant	Advantage	Disadvantage
Inactivated	Whole virus; (i) Inactivated by formaldehyde or gamma irradiation	Mice	IM	Alum and CpG ODN	(i) Excellence in neutralizing Ab induction	(i) Possible cause hypersensitivity-type lung
					(ii) Can be combined with different adjuvant	(ii) Possible Th2-bias
						(iii) Cannot employ cell-mediated immunity
Live-attenuated virus	Mutant MERS-CoV and SARS-CoV	Mice, rhesus macaques	IN, IP	—	(i) Excellence in the induction of T and B cell responses	(i) Risk of relapse
					(ii) Site-directed mutagenesis can be tailor-made	(ii) Cold chain required
						(iii) Not suitable or sensitive population such as infants, immunocompromised, or elderly individuals
Subunit	Full-length spike, S1, RDB, nucleocapsid; (i) Formulated with various adjuvants and/or fused with Fc	Mice, rhesus macaques	SC, IM, IN	MF59, Ontanide, Freund’s adjuvant, alum, monophosphoryl lipid A, Montanide ISA51, CpG ODN	(i) High safety profile	(i) Need appropriate adjuvant
					(ii) Continuous production	(ii) Cost-effectiveness may change
					(iii) Induction of high titers of neutralizing antibodies
					(iv) Local mucosal immune responses were observed in mice immunized through IN route
DNA	Full-length spike or S1; (i) IM follow by electroporation	Mice, camels and rhesus macaques	IM	Without adjuvant	(i) Fast production	(i) Efficient delivery system required
					(ii) Simple design and manipulation	(ii) Induce lower immune responses when compared with a live vaccine
					(iii) Initiate both B and T cell responses
Viral vector	Full-length spike or S1; (i) Vector used: ChAd or MVA	Mice, Bactrian camels	IM	CD40L	(i) Excellence in immune induction	(i) Different inoculation routes may produce different immune responses
						(ii) Possible TH2 bias
Virus-like particles	RDB, S, or coexpressing of S1, M, and E	Rhesus macaques, mice	IM	Alum, poly(I:C) CpG ODN	(i) Multimeric antigen display	(i) Need optimum assembly condition
					(ii) Maintain virus particle structure

RBD: a receptor-binding domain in S1; MVA: modified vaccinia virus Ankara; ChAdOx1: chimpanzee adenovirus; IM: intramuscular; IN: intranasal; IP: intraperitoneal; SC: subcutaneous.