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The Humoral Immune Response to HCV: Understanding is Key to Vaccine Development.

Cashman SB, Marsden BD, Dustin LB - Front Immunol (2014)

Bottom Line: The low cost and high benefit of vaccines have made them the backbone of modern public health strategies, and the fight against HCV will not be won without an effective vaccine.In addition, we discuss specific epitopes within HCV's envelope glycoproteins that are targeted by neutralizing antibodies.Understanding what prompts or prevents a successful immune response leading to viral clearance or persistence is essential to designing a successful vaccine.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford , Oxford , UK.

ABSTRACT
Hepatitis C virus (HCV) remains a global problem, despite advances in treatment. The low cost and high benefit of vaccines have made them the backbone of modern public health strategies, and the fight against HCV will not be won without an effective vaccine. Achievement of this goal will benefit from a robust understanding of virus-host interactions and protective immunity in HCV infection. In this review, we summarize recent findings on HCV-specific antibody responses associated with chronic and spontaneously resolving human infection. In addition, we discuss specific epitopes within HCV's envelope glycoproteins that are targeted by neutralizing antibodies. Understanding what prompts or prevents a successful immune response leading to viral clearance or persistence is essential to designing a successful vaccine.

No MeSH data available.


Related in: MedlinePlus

HCV envelope glycoprotein 2 surface representation. E2 is a globular protein with three regions of hypervariablity – HVR1, HVR2, and intergenotypic variable region – shown in green. Domains whose structures are currently unknown are depicted as shapes apart from the structure. HVR1 is predicted to mask a hydrophobic region that is sensitive to nAbs. E2’s broadly neutralizing face, where many broadly neutralizing Abs bind, comprises CD81-binding loop (in red), residues 421–453 (in orange), residues 502–520 (in pink), and residues 412–421 (in purple). The possible positions of some glycans are shown as stick and ball figures. E2 structure obtained from PDB (4MWF) (45).
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Figure 1: HCV envelope glycoprotein 2 surface representation. E2 is a globular protein with three regions of hypervariablity – HVR1, HVR2, and intergenotypic variable region – shown in green. Domains whose structures are currently unknown are depicted as shapes apart from the structure. HVR1 is predicted to mask a hydrophobic region that is sensitive to nAbs. E2’s broadly neutralizing face, where many broadly neutralizing Abs bind, comprises CD81-binding loop (in red), residues 421–453 (in orange), residues 502–520 (in pink), and residues 412–421 (in purple). The possible positions of some glycans are shown as stick and ball figures. E2 structure obtained from PDB (4MWF) (45).

Mentions: Two recent reports have shed light on the structure of E2 (45, 46). Most surprisingly, E2 did not adopt the expected, highly extended conformation of class II fusion envelope protein like other members of Flaviviridae, such as Tick-borne encephalitis virus or West Nile virus; instead, HCV E2 was found to be compact and globular (Figure 1), with a central beta sandwich surrounded front and back by short alpha helices, loops, beta sheets, and regions lacking organized structure (45, 46).


The Humoral Immune Response to HCV: Understanding is Key to Vaccine Development.

Cashman SB, Marsden BD, Dustin LB - Front Immunol (2014)

HCV envelope glycoprotein 2 surface representation. E2 is a globular protein with three regions of hypervariablity – HVR1, HVR2, and intergenotypic variable region – shown in green. Domains whose structures are currently unknown are depicted as shapes apart from the structure. HVR1 is predicted to mask a hydrophobic region that is sensitive to nAbs. E2’s broadly neutralizing face, where many broadly neutralizing Abs bind, comprises CD81-binding loop (in red), residues 421–453 (in orange), residues 502–520 (in pink), and residues 412–421 (in purple). The possible positions of some glycans are shown as stick and ball figures. E2 structure obtained from PDB (4MWF) (45).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4226226&req=5

Figure 1: HCV envelope glycoprotein 2 surface representation. E2 is a globular protein with three regions of hypervariablity – HVR1, HVR2, and intergenotypic variable region – shown in green. Domains whose structures are currently unknown are depicted as shapes apart from the structure. HVR1 is predicted to mask a hydrophobic region that is sensitive to nAbs. E2’s broadly neutralizing face, where many broadly neutralizing Abs bind, comprises CD81-binding loop (in red), residues 421–453 (in orange), residues 502–520 (in pink), and residues 412–421 (in purple). The possible positions of some glycans are shown as stick and ball figures. E2 structure obtained from PDB (4MWF) (45).
Mentions: Two recent reports have shed light on the structure of E2 (45, 46). Most surprisingly, E2 did not adopt the expected, highly extended conformation of class II fusion envelope protein like other members of Flaviviridae, such as Tick-borne encephalitis virus or West Nile virus; instead, HCV E2 was found to be compact and globular (Figure 1), with a central beta sandwich surrounded front and back by short alpha helices, loops, beta sheets, and regions lacking organized structure (45, 46).

Bottom Line: The low cost and high benefit of vaccines have made them the backbone of modern public health strategies, and the fight against HCV will not be won without an effective vaccine.In addition, we discuss specific epitopes within HCV's envelope glycoproteins that are targeted by neutralizing antibodies.Understanding what prompts or prevents a successful immune response leading to viral clearance or persistence is essential to designing a successful vaccine.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford , Oxford , UK.

ABSTRACT
Hepatitis C virus (HCV) remains a global problem, despite advances in treatment. The low cost and high benefit of vaccines have made them the backbone of modern public health strategies, and the fight against HCV will not be won without an effective vaccine. Achievement of this goal will benefit from a robust understanding of virus-host interactions and protective immunity in HCV infection. In this review, we summarize recent findings on HCV-specific antibody responses associated with chronic and spontaneously resolving human infection. In addition, we discuss specific epitopes within HCV's envelope glycoproteins that are targeted by neutralizing antibodies. Understanding what prompts or prevents a successful immune response leading to viral clearance or persistence is essential to designing a successful vaccine.

No MeSH data available.


Related in: MedlinePlus