Table 1.

Vaccines for treating Ebola virus disease.

S. No.	Type of vaccine platform	Vaccine	Adjuvant/mode of delivery	Model	Antigen	Inference	Reference
1	Inactivated vaccine	Rabies virus based on inactivated vaccine (FILORAB1)	Glucopyranosyl lipid A	Cyanomolgus and rhesus monkeys	GP	100% protection against lethal Ebola virus (EBOV) challenge, with no to mild clinical signs of disease	Johnson et al. (108)
		Virulent EBOV	Formalin inactivation/heat inactivation	Guinea pig	Complete virus as antigen	Reduction in mortality	Lupton et al. (53)
2	Attenuated vaccine	Live replication-competent EBOV and rabies virus-based bivalent vaccine	Direct inoculation of live-attenuated vaccine	Rhesus macaques	GP	100% protection from lethal challenge	Blaney et al. (109)
3	DNA vaccine	Multiagent filovirus DNA vaccine containing GP of Zaire, Sudan, and Marburg virus (MARV)	Electrical stimulation at an amplitude of 250 V/cm using TriGrid™ electroporation device	BALB/c mice	GP	100% protection from lethal challenge	Grant-Klein et al. (110)
					Mutant GP
		Synthetic polyvalent-filovirus DNA vaccine against Zaire, Sudan, and MARV	pVAX1 mammalian expression vectors, injected intradermally with 200 µg DNA	Guinea pigs	Codon-optimized GP	100% protection from lethal challenge	Shedlock et al. (111)
		DNA vaccine against EBOV	Intramuscular electroporation (IM-EP) 500 µg dose	Rhesus macaques	Codon-optimized GP	86% protection	Grant-Klein et al. (59)
		DNA encoding Zaire and Sudan glycoproteins	4 mg dose in 1 ml volume	Human healthy adults	Wild-type GP	Antibody response to the Ebola Zaire glycoprotein generated	Kibuuka et al. (60)
4	mRNA vaccine	mRNA molecule encapsulated in a lipid nanoparticle (LNP) formulation	0.2 mg/ml	Guinea pigs	A human Igκ signal peptide or the wild-type signal peptide sequence of GP attached to GP	Potency of mRNA vaccines is enhanced by LNP	Meyer et al. (49)
5	Ebola virus-like particles (VLPs)	pWRG7077 plasmid vectors encoding for Ebola VP40 and GP	10 µg of eVLPs	Balb/c mice	GP and matrix protein (VP40) in mammalian cells	Dose-dependent protection against lethal challenge	Warfield et al. (112)
		MARV GP and EBOV VP40 or vice-versa	Intramuscular vaccination with 100 µg of VLPs + 200 µl RIBI adjuvant	Strain 13 guinea pigs	GP and VP40	Homologous GP is essential and sufficient for protection against lethal challenge with homologous virus	Swenson et al. (113)
		pWRG7077 plasmid vectors encoding for GP, NP, and VP40	3 intramuscular injections of 250 µg of eVLPs + 0.5 ml of RIBI adjuvant	Cynomolgus macaques	GP, NP, and VP40	All animals were protected without showing signs of clinical illness	Warfield et al. (114)
		293T cells transfected with	VLP containing 10 µg GP	C57BL/6 mice	GP + VP40	VLP-mediated anti-EBOV immunity in B cell-deficient mice	Cooper et al. (66)
6	Vaccinia virus-based vaccine	Modified vaccinia virus Ankara-Bavarian Nordic® (MVA-BN) co-expressing VP40 and glycoprotein (GP) of EBOV Mayinga and NP of Taï Forest virus	Intramuscular or intravenous application of 108 TCID50 of MVA-BN-EBOV-GP or MVA-BN-EBOV-VLP	CBA/J mice	GP + VP40	Production of non-infectious EBOV-VLPs	Schweneker et al. (95)
		Modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona GP and VP40	1 × 108 TCID50	Rhesus macaques	GP + VP40	100% protection with single or prime/boost vaccination	Domi et al. (115)
7	Venezuelan equine encephalitis virus (VEEV)-based vaccine	VEEV-like replicon particles (VRP)	107 IU VRP	Strain 2 or strain 13 guinea pigs	NP or GP	NP-VRP and GP-VRP immunized animals completely protected against lethal challenge	Pushko et al. (116)
		VRP expressing SUDV GP + EBOV GP	1010 focus-forming units	Cynomolgus macaques	GP (EBOV + SUDV)	100% protection against intramuscular challenge with either SUDV or EBOV	Herbert et al. (68)
8	Cytomegalovirus (CMV)-based vaccines	CD8+ T cell epitope from EBOV NP (VYQVNNLEEIC) cloned in mouse CMV vector	5 × 105 plaque forming units	C57BL/6 mice	NP	High levels of long-lasting (>8 months) CD8+ T cells are produced	Tsuda et al. (117)
9	Kunjin virus-based vaccine	Kunjin virus VLPs expressing GP	5 × 106 VLPs	Dunkin–Hartley guinea pigs	GP	More than 75% survival of animals post challenge	Reynard et al. (118)
10	Paramyxovirus-based vaccines	Human parainfluenza virus type 3 (HPIV3) clone containing GP	107 plaque-forming units	Rhesus monkeys	GP	Double immunization protected animals	Bukreyev et al. (119)
		Newcastle disease virus clone containing GP	107 plaque-forming units	Rhesus monkeys	GP	NDV/GP is highly attenuated for replication in the respiratory tract of immunized animals and developed GP-specific mucosal IgA antibodies	DiNapoli et al. (120)
11	Adenovirus-based vaccines	Adenovirus (rAd5) vaccine GP	2 × 109 virus particle	Phase I human study	GP	Antigen specific humoral and cellular immune responses were generated	Ledgerwood et al. (121)
		Adenovirus (ChAd3) vaccine boosted with MVA	Priming dose 2.5 × 1010 PFU of ChAd3 and a boosting dose of 1.5 × 108 PFU of MVA	Healthy adult volunteers	GP	Elicited B-cell and T-cell immune responses	Ledgerwood et al. (91)
		Chimpanzee serotype 7 adenovirus vaccine expressing GP (AdC7-GP)	Prime boosting with AdC7-GP (1 × 1010) and boosting with 20 mg Drosophila S2 cells expressed truncated GP	BALB/c mice	GP	Long-lasting high-titer neutralizing antibodies production in mice and efficiently prevented luciferase-containing reporter EBOV-like particle entry even at 18 weeks post-immunization	Chen et al. (90)
12	Vesicular stomatitis virus (VSV)-based vaccines	VSV GP replaced with EBOV GP	2 × 107 PFU	Healthy adult volunteers	GP	Anti-Ebola immune responses were documented	Regules et al. (82)
		VSV GP replaced with EBOV GP	3 × 105 PFU	Healthy adult volunteers	GP	Lowered antibody responses observed with vaccine associated side effects like vaccine-induced arthritis and dermatitis	Agnandji et al. (122)
13	Semliki forest virus based vaccines	From DNA-launched replicons (DREP)-eGFP vector, eGFP replaced with GP and NP to make DREP-GP and DREP-VP40 vectors, respectively	10 µg plasmid DNA	Balb/c mice	GP + VP40	EBOV filamentous VLPs were observed in the supernatant of cells resulting from co-expression of GP and VP40 and post immunization, specific humoral accompanied with a mixed Th1/Th2 cellular immune response was obtained	Ren et al. (69)
14	Liposome-encapsulated vaccine	Liposome-encapsulated irradiated EBOV-Zaire (6 × 106 rads of γ-irradiation from a 60Co source)	Intravenous inoculation of 1.0 ml dose containing 194 µg of irradiated EBOV Zaire + 100 µg of lipid A	BALB/c mice and Cynomolgus monkeys	All native EBOV antigens	All mice protected, however the immunization failed to protect Cynomolgus monkeys	Rao et al. (54)