Table 1.

E2 and E1E2 immunogen designs tested in vivo.

Design(s)	In Vivo Data	Viruses Tested for Neutralization 1	Results 2	Reference
Cyclized domain E peptides, truncated E2 core with additional domain E and HVR1 removed	Mouse	Homologous HCVpp: H77 Heterologous HCVpp: genotypes 1b, 4a	Neutralized H77 in HCVpp assays	[77]
E2 core with proline mutations in domain D or E, glycosylation of domain A, HVR1 removed	Mouse	Homologous HCVpp: H77 Heterologous HCVpp: genotypes 1b, 2a, 2i, 4a	Increased neutralization of heterologous strains in HCVpp assays	[97]
E2 core with truncated and designed HVR2, displayed on nanoparticles	Mouse	Homologous HCVpp: H77 Heterologous HCVpp: genotypes 1a, 2a, 5a	Increased neutralization of H77 in HCVpp assays	[98]
Cyclized and conjugated domain E peptide	Mouse	Homologous HCVcc: H77 Heterologous viruses: not tested	Antibody isolated from mice non-neutralizing in HCVcc assays	[75]
E2 core with eight cysteines mutated	Mouse	Homologous HCVpp: H77 Heterologous viruses: not tested	No neutralization of H77 in HCVpp assays	[99]
E1E2 ectodomains oligomerized with C4b-binding protein IMX313P	Mouse	Homologous virus: not tested Heterologous HCVpp: genotypes 1a, 1b, 2a, 2b, 3a, 4, 5, 6	Neutralized most strains in HCVpp assays	[100]
E2 core with HVR1 and HVR2 removed, IgVR deglycosylated, and displayed on nanoparticles	Mouse	Homologous HCVpp: H77 Heterologous HCVpp: genotype 1b	Increased neutralization of H77 in HCVpp assays	[101]
E2 core fused to ferritin	Mouse	Homologous HCVcc: Con1 Heterologous HCVcc: genotypes 1a, 1b, 2a, 3a, 4a, 5a, 7a	Increased neutralization of strains in HCVcc assays	[102]
Synthetic consensus of E2 core from genotype 1 sequences	Guinea pig	Homologous HCVpp: NotC1 Heterologous HCVpp: genotypes 1a, 1b, 2a, 3	Increased neutralization of H77 in HCVpp assays	[103]
E2 core with variable regions removed and seven cysteines mutated	Guinea pig	Homologous HCVpp: H77 Heterologous HCVcc: genotypes 2a, 3a, 5a	Neutralized H77 HCVpp, limited neutralization of HCVcc	[104]
Combination of two HVR1 peptides	Mouse	Homologous HCVpp: C47 Heterologous HCVpp: genotypes 1a, 1b, 2a, 3a, 4a, 5a, 6a	Neutralized strains in HCVpp assays	[105]
E2 with mutated N-glycan sites and HVR1 removed	Mouse	Homologous HCVcc: Jc1 Heterologous HCVcc: genotype 5a Heterologous HCVpp: genotype 1a	Neutralized Jc1 HCVcc, H77 HCVpp	[106]
E2 epitopes from domains B, D, and E, and HVR1 mimotope displayed on HBV-S VLPs	Mouse	Homologous virus: not tested Heterologous HCVpp and HCVcc: genotypes 1a, 1b, 2a	Neutralized strains in HCVpp and HCVcc assays	[91]
E2 epitopes from domains B-E displayed on HBV-S VLPs	Mouse	Homologous virus: not tested Heterologous HCVcc: genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, 6a	IgGs purified from sera neutralized some strains in HCVcc assays	[96]
E1E2 ectodomains with C-terminal leucine zipper as scaffold, furin cleavage site	Mouse	Homologous HCVpp: H77 Heterologous viruses: not tested	Neutralized H77 in HCVpp assays	[107]

¹ Homologous virus is listed by strain name; heterologous viruses are listed by genotype and subtype when known. ² Summary of measured neutralization induced by design, or improvement in neutralization over non-designed control, if measured by the authors. Unless otherwise noted, results refer to serum neutralization.