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Hepatitis C Virus I pp 331–357Cite as

B Cell Responses and Control of HCV Infection

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Abstract

Humoral immunity is the primary correlate of protection for most preventive vaccines. For hepatitis C virus (HCV), early animal studies provided support for the importance of virus neutralizing antibodies to facilitate clearance of infection. The development of retroviral pseudotype particles expressing HCV E1E2 glycoproteins (HCVpp), infectious cell culture-derived HCV virions (HCVcc), and small animal models of acute HCV infection have made possible the measurement of in vitro and in vivo antibody-mediated virus neutralization. Their applications in multiple studies clearly established the importance of neutralizing antibodies in controlling HCV infection. However, the virus has devised a number of decoys of highly immunogenic regions associated with viral escape or non-neutralizing antibodies that deflect the immune response from less immunogenic conserved regions mediating virus neutralization that are not associated with viral escape or escape with compromised fitness. The focus of this review is on the immunogenic determinants on E2, which are roughly segregated into the hypervariable region 1 (HVR1), and five clusters of overlapping epitopes, designated as antigenic domains A-E. A detailed understanding of conserved neutralizing epitopes within these antigenic domains that are not associated with escape and how other antigenic regions or decoys serve as diversions of the immune response and/or elicit antibodies that negatively modulate broadly neutralizing antibodies will provide a roadmap in rational design for an HCV vaccine.

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Abbreviations

aa:

Amino acids

CI:

Combination index

DAA:

Direct acting antivirals

HCV:

Hepatitis C virus

HCVcc:

Cell culture-derived HCV virions

HCVpp:

HCV pseudoparticles

HDL:

High-density lipoprotein

HMAb:

Human monoclonal antibody

HVR1:

Hypervariable region 1

IC50 :

50 % inhibitory concentration of the antibody

LDLR:

Low density lipoprotein receptor

MOI:

Multiplicity of infection

SR-B1:

Scavenger receptor class B type 1

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Acknowledgements

We thank Yili Li and Adam Wang for preparing Fig. 5. This work was supported in part by PHS grants R41-AI108024 and U19-AI123862 (SKHF), and MPower (RAM and TRF).

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Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Zhen-Yong Keck & Steven K. H. Foung

  2. Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA

    Thomas R. Fuerst

  3. W. M. Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA

    Roy A. Mariuzza

  4. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA

    Thomas R. Fuerst & Roy A. Mariuzza

  5. Stanford Blood Center, 3373 Hillview Avenue, Palo Alto, CA, 94304, USA

    Steven K. H. Foung

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  1. Zhen-Yong Keck
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  2. Thomas R. Fuerst
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  3. Roy A. Mariuzza
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  4. Steven K. H. Foung
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Correspondence to Steven K. H. Foung .

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Editors and Affiliations

  1. National Institute of Infectious Diseases, Tokyo, Tokyo, Japan

    Tatsuo Miyamura

  2. Departments of Medicine and Microbiology & Immunology , The University of North Carolina, Chapel Hill, North Carolina, USA

    Stanley M. Lemon

  3. Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA

    Christopher M. Walker

  4. National Institute of Infectious Diseases, Tokyo, Tokyo, Japan

    Takaji Wakita

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Keck, ZY., Fuerst, T.R., Mariuzza, R.A., Foung, S.K.H. (2016). B Cell Responses and Control of HCV Infection. In: Miyamura, T., Lemon, S., Walker, C., Wakita, T. (eds) Hepatitis C Virus I. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56098-2_14

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