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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

Mechanisms of HCV evasion of the humoral immune system. HCV has developed several strategies for evading the humoral immune system. (A) A high rate of replication using a polymerase that lacks any proofreading mechanism leads to generation of a rapidly changing quasispecies. (B) The highly immunogenic HVR1 masks a hydrophobic region that is sensitive to nAbs. (C) E2 is heavily glycosylated, containing between 9 and 11 N-linked glycans (in green) that mask much of the surface of E2 from nAbs. (D) The close association between HCV and lipoprotein effectively conceals the lipoviral particle from nAbs. (E) HCV may bypass the extracellular space and nAbs by spreading cell-to-cell. (F) Interfering antibodies can disrupt the action of nAbs by binding to non-neutralizing sites and masking neutralizing sites nearby.
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Figure 2: Mechanisms of HCV evasion of the humoral immune system. HCV has developed several strategies for evading the humoral immune system. (A) A high rate of replication using a polymerase that lacks any proofreading mechanism leads to generation of a rapidly changing quasispecies. (B) The highly immunogenic HVR1 masks a hydrophobic region that is sensitive to nAbs. (C) E2 is heavily glycosylated, containing between 9 and 11 N-linked glycans (in green) that mask much of the surface of E2 from nAbs. (D) The close association between HCV and lipoprotein effectively conceals the lipoviral particle from nAbs. (E) HCV may bypass the extracellular space and nAbs by spreading cell-to-cell. (F) Interfering antibodies can disrupt the action of nAbs by binding to non-neutralizing sites and masking neutralizing sites nearby.

Mentions: Neutralizing antibodies are induced during HCV infection, which in some patients contribute to the spontaneous clearance of infection, yet the majority of infected patients progress to chronicity. How does HCV evade the humoral immune response to progress to chronicity? Several mechanisms may contribute to evasion of sterilizing Ab-mediated clearance. These include sequence changes, decoy epitopes, epitope masking, lipid shielding, induction of interfering antibodies, and the ability to move from one cell to another in a neutralization-resistant fashion (Figure 2).


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

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

Mechanisms of HCV evasion of the humoral immune system. HCV has developed several strategies for evading the humoral immune system. (A) A high rate of replication using a polymerase that lacks any proofreading mechanism leads to generation of a rapidly changing quasispecies. (B) The highly immunogenic HVR1 masks a hydrophobic region that is sensitive to nAbs. (C) E2 is heavily glycosylated, containing between 9 and 11 N-linked glycans (in green) that mask much of the surface of E2 from nAbs. (D) The close association between HCV and lipoprotein effectively conceals the lipoviral particle from nAbs. (E) HCV may bypass the extracellular space and nAbs by spreading cell-to-cell. (F) Interfering antibodies can disrupt the action of nAbs by binding to non-neutralizing sites and masking neutralizing sites nearby.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Mechanisms of HCV evasion of the humoral immune system. HCV has developed several strategies for evading the humoral immune system. (A) A high rate of replication using a polymerase that lacks any proofreading mechanism leads to generation of a rapidly changing quasispecies. (B) The highly immunogenic HVR1 masks a hydrophobic region that is sensitive to nAbs. (C) E2 is heavily glycosylated, containing between 9 and 11 N-linked glycans (in green) that mask much of the surface of E2 from nAbs. (D) The close association between HCV and lipoprotein effectively conceals the lipoviral particle from nAbs. (E) HCV may bypass the extracellular space and nAbs by spreading cell-to-cell. (F) Interfering antibodies can disrupt the action of nAbs by binding to non-neutralizing sites and masking neutralizing sites nearby.
Mentions: Neutralizing antibodies are induced during HCV infection, which in some patients contribute to the spontaneous clearance of infection, yet the majority of infected patients progress to chronicity. How does HCV evade the humoral immune response to progress to chronicity? Several mechanisms may contribute to evasion of sterilizing Ab-mediated clearance. These include sequence changes, decoy epitopes, epitope masking, lipid shielding, induction of interfering antibodies, and the ability to move from one cell to another in a neutralization-resistant fashion (Figure 2).

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