From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection

Figures & data

Table 1. Diverse vaccination approaches tested against Leishmania

Type of vaccine	Mechanism	Manifestation	Challenge	Advantages	Disadvantages	References
Killed Leishmania	Polyvalent whole killed Leishmania	CL	Made with 5 to 18 species of Leishmania	Safe and immunogenic. Positive LST in 78.4% within 3 months	Lack of circulating antibodies	[131–134]
	BCG as adjuvant to killed Leishmania	CL	L. braziliensis, L. guyanensis, L. amazonensis, L. major	Safe. IFN-γ induction in vitro. Positive LST in vivo	Future protection not associated with vaccination	[135–147]
Subunit and Recombinant Vaccines	Recombinant LEISH-F1, LIESH-F2 and LEISH-F3	VL and CL	L. donovani, L. infantum, L. major	Safe and immunogenic	Weak cell-mediated response. Need to be administered together with an adjuvant	[155–157].
	Sand fly saliva antigens: LJM19 and LJL143 from L. longipalpis and PdSP15 from P. duboscqui	VL and CL	L. infantum, L. major	Immunogenic and effective. Induction of cell-mediated immune response without the addition of an adjuvant	Not reported	[167–172]
DNA Vaccines	RNA vaccine expressing LEISH-F2	VL	L. donovani	Protection against infection. Induction of potent local innate and Th1 immune responses	Need for a careful formulation to protect RNA from degradative enzymes and allow its delivery across the cell membrane. Possibly liposome formulation	[173]
	gp63 DNA vaccine	VL and CL	L. donovani, L. major, L. mexicana	Safe. Induction of Th1 response. Protection against L. major and partially against L. mexicana in murine models	Weak immunogenicity in canine VL	[177,184,186,187]
	LACK DNA vaccine	VL and CL	L. donovani, L. infantum and L. major	Varied protection in canine and murine models. Induction of Th1 response	Does not protect against L. donovani	[175,190–193]
Live-attenuated Vaccines	BT1-/- L. donovani	VL	L. donovani	Protective immunity, IFN-γ production. Less infective than the WT	Still detected in liver and spleen after 4 weeks	[213]
	Ldp27-/- L. donovani		L. donovani, L. brazilensis and L. major	Reduction of parasite loads. Long- and short-term protection. Increased Th1 response, protective immunity against CL and VL. Parasites fail to survive inside the macrophages	Few surviving parasites in liver after 13 weeks	[214,215]
	HSP70-II null L. infantum	VL and CL	L. infantum, L. amazonensis and L. major	Reduction of parasite loads. Induction protective inflammatory responses. Protection against CL	Inability to control the infection in spleen and BM in VL model	[216–219]
	KHARON1 null mutants L. infantum	VL	L. infantum	Cell cycle arrest from the parasite. Unable to sustain experimental macrophage infection. Production of IgG and IL-17. Protection against the WT	Long lasting protection is still not demonstrated	[220]
	Cen-/- L. major and L. donovani	VL and CL	L. donovani and L. major	Safe, immunogenic, and protective in mice and hamsters. Parasites fail to survive inside the macrophages. Does not survive in vector’s gut	There might be safety issues in immunocompromised individuals, however this has not yet been demonstrated	[118,221,222]

Select examples of Leishmania vaccines demonstrate the general mechanism, the clinical manifestation and species used for challenge, as well as the advantages and disadvantages of each approach.

CL: Cutaneous leishmaniasis; VL: visceral leishmaniasis; LST: Leishmanin skin test; BCG: of Bacillus Calmette Guerin; PSG: promastigote secretory gel; BT1: Biopterin transporter gene; HSP: Heat shock protein Cen: centrin gene.

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