Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure

Table 2 Candidate immunotherapies for chronic hepatitis B virus infection

	Compound	Class and action	Phase of development	Ref. or trial number
TLR agonists	GS-9620 (or Vesatolimod)	TLR-7 agonist	Phase II	Janssen et al[112] and Boni et al[113]
	RO7020531 (RG7854)	TLR-7 agonist	Phase II	Luk et al[116]
	JNJ-64794964	TLR-7 agonist	Phase I	Wu et al[117]
	APR002	TLR-7 agonist	Preclinical	Korolowizc et al[115]
	T7-EA	TLR-7 agonist	Preclinical	Hu et al[118]
	GS-9688 (or Selgantolimod)	TLR-8 agonist	Phase II	Mackman et al[121] and Janssen et al[122]
	ImmunoTAC™	ASGR1-TLR8 agonist conjugate	Preclinical	Baum et al[123]
RIG-I, NOD agonists	SB9200 (or Inarigivir)	RIG-I/NOD-2 agonist	Phase II	Yuen et al[129]
STING agonists	DMXAA (or Vadimezan or ASA404)	STING agonist	Preclinical	Guo et al[132]
T-cell engineering	TCR-engineered T cells	TCR-specific for MHC-I restricted HBV epitopes	Phase I	NCT03899415 NCT02719782 NCT02686372
	S-CAR engineered T cells	CAR targeting envelope proteins	Preclinical	Festag et al[145]
	IMC-I109V	ImmTAV targeting HLA-A restricted HBV epitopes	Phase II	EudraCT2019-004212-64
	ImmTAV-HLA-E	ImmTAV targeting HBV epitopes presented by HLA-E	Preclinical	Leonard et al[151]
Immune checkpoint inhibitors	Nivolumab	Monoclonal antibodyPD-1 inhibitor	Phase Ib	Gane et al[155]
	ASC22 (Envafolimab)	Monoclonal antibodyPD-L1 inhibitor	Phase II	NCT04465890
	HSV-1 glycoprotein D (gD)	BTLA-HVEM pathway inhibitor	Preclinical	Hasanpourghadi et al[158]
	APG-1387	IAP antagonist	Phase II	Zhang et al[159]
Vaccines	INO-1800	DNA vaccine	Phase I	NCT02431312
	HB110	DNA vaccine	Phase I	Yoon et al[164]
	JNJ-64300535	DNA vaccine	Phase I	NCT03463369
	AIC649	Viral vector vaccine (iPPVO)	Phase I	Addy et al[167]
	TG1050	Viral vector vaccine (Ad5)	Phase Ib	Zoulim et al[168]
	VTP-300	Viral vector vaccine (ChAdOx1)	Phase I	Vaccitech[169]
	HepTcell	T cell vaccine	Phase II	Lim et al[171] and Altimmune[172]
	GS-4774	Yeast-based, T-cell vaccine	Phase II	Boni et al[173]
	Chimigen® HBV (C-HBV)	Immune complex vaccine	Preclinical	Ma et al[177]
	YIC (HBsAg-HBIG)	Vaccine based on yeast-derived immune complexes	Phase II	Zhou et al[178] and Xu et al[179]
	ABX-203 (or Nasvac)	HBsAg and HBcAg	Phase III	Al Mahtab et al[183] and Yoshida et al[184]
	VBI-2601 (or BRII-179)	eVLP-based vaccine	Phase II	ACTRN-12619001210167
	NP-preS1	Nanoparticle-based vaccine	Preclinical	Wang et al[190]

Ad5: Adenovirus serotype 5; ASGR1: Asialoglycoprotein receptor 1; BTLA-HVEM: B and T lymphocyte attenuator/herpes virus entry mediator; CAR: Chimeric antigen receptor; ChAdOx1: Chimpanzee adenovirus Oxford 1; eVLP: enveloped virus-like particle; HBcAg: Hepatitis B core antigen; HBsAg: Hepatitis B surface antigen ; HBV: Hepatitis B Virus; HLA: Human leukocyte antigen; HSV: Herpes simplex virus; IAP: Inhibitors of apoptosis protein; ImmTAV: Immunomobilizing monoclonal T cell receptors against virus; iPPVO: Inactivated Parapoxvirus ovis; MHC: Major histocompatibility complex; NOD: Nucleotide-binding and oligomerization domain; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; RIG-I: Retinoic acid-inducible gene I; STING: Stimulator of IFN genes; TCR: T cell receptor; YIC: Yeast-derived immune complexes