Table 1.

Hepatitis C virus proteins, their function, role in immune response and position in different hepatitis C virus vaccines

HCV proteins	Genetic stability	Function	Role in immune responses	HCV vaccines
Structural proteins
Core (C): P22	Stable	Major component of viral nucleocapsid	Target for neutralizing Ab and CMI	Synthetic peptides vaccines; e.g., VAL-44 in mice[66]
		Binds viral RNA during assembly	Block the innate immune response	Recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein in mice[70]
				DNA vaccine: CIGB-230 in humans[100]
E1: gp 35 envelope glycoproteins	High degree of genetic diversity	Receptor binding and HCV entry into target cells	Target for nAbs	The primary immunogen for vaccinology[8,78]
E2: gp 70 envelope glycoproteins			Continuous variation allowing viral escape of HCV specific CD8 T cells and nAb and exhaustion of CD8 cell in chronic HCV infection[101]	Recombinant HCV E1E2 glycoproteins in chimpanzees/humans -core/E1/E2 (CIGB-230) in human[13,96,100]
			Target for pan-genotypic drug therapy	Fusion proteins containing the entire HCV E1 or E2 sequence that is efficiently co-assembled with the HBV S into particles[82]
				E1E2MF59 HCV DNA vaccine in human[8]
Non-structural proteins
NS1: p7 small polypeptide	Stable	Ion channel localized to plasma membrane	No assigned role	-
NS2: p23		Protease transmembrane protein	NS2/3 cleavage is required for persistent viral infection in chimpanzees	Full-length HCV NS2 protein DNA vaccine in mice[102]
HCV Proteins	Genetic stability	Function	Role in immune responses	HCV vaccines
NS3: p70		Bifunctional serine protease and RNA helicase	Act as a critical immune regulator during HCV infection[102]	Recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein in mice[70]
NS4A: p8	Stable	Protease cofactor	Block the innate immune response[103]	Ad vector vaccine ( NS3-NS5B in chimpanzees/humans[25,87]
				DNA vaccine: e.g.,
				Chron Vac-c in mice with multiple epitopes; NS3/4a, NS4b, NS5a, and NS5b in Rhesus macaques[84]
				ChronVac-C- NS3/4A-expressing DNA vaccine in human in human[73]
				DNA plasmid vaccine encoding NS3/4a, NS4b, NS5a, and NS5b in Rhesus macaques[28]
NS4B: p27	Stable	Proteins	Block the innate immune response[103]	Synthetic peptides vaccines; e.g., VAL-44[66]
		Components of the viral replicase complex		DNA vaccine with multiple epitopes; NS3/4a, NS4b, NS5a, and NS5b in Rhesus macaques[28]
NS5A:p56/58	Stable	Cofactor for NS5B	Block the innate immune response[103]	In mice: Synthetic peptides vaccines; e.g., VAL-44[67]-NS5a-loaded DCs[89]
		Regulate response to INF-α treatment	Modulate the cellular environment to favor virus replication and persistence[104]
			Protects cells from TNF-α-mediated apoptotic death[104]	in Rhesus macaques: DNA vaccine with multiple epitopes; NS3/4a, NS4b, NS5a, and NS5b[28]
NS5B: p68	Stable	RNA dependent polymerase	No assigned role	DNA vaccine with multiple epitopes; NS3/4a, NS4b, NS5a, and NS5b in Rhesus macaques[28]
				Ad vector vaccine (NS3-NS5B in chimpanzees/humans)[97]

HCV: Hepatitis C virus.