Specific Antibodies Induced by Immunization with Hepatitis B Virus-Like Particles Carrying Hepatitis C Virus Envelope Glycoprotein 2 Epitopes Show Differential Neutralization Efficiency

Czarnota, Anna; Offersgaard, Anna; Pihl, Anne Finne; Prentoe, Jannick; Bukh, Jens; Gottwein, Judith M.; Bieńkowska-Szewczyk, Krystyna; Grzyb, Katarzyna

doi:10.3390/vaccines8020294

Cited by 17 publications

(19 citation statements)

References 68 publications

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“…S9). Interestingly, an epitope 412-425 comprising such residues (423 and 425) was shown in a recent study to be capable of inducing potent neutralizing antibodies against multiple HCV genotypes including 1a and 1b [52]. Hence, targeting these residues may assist in eliciting an effective immune response against both subtypes.…”

Section: Resultsmentioning

confidence: 99%

Evolutionary modelling of HCV subtypes provides rationale for their different disease outcomes

Zhang

McKay

2021

Preprint

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Hepatitis C virus (HCV) is a leading cause of liver-associated disease and liver cancer. Of the major HCV subtypes, patients infected with subtype 1b have been associated with having a higher risk of developing chronic infection, cirrhosis and hepatocellular carcinoma. However, underlying reasons for this increased disease severity remain unknown. Here, we provide an evolutionary rationale, based on a comparative study of fitness landscape and in-host evolutionary models of the envelope glycoprotein 2 (E2) of HCV subtypes 1a and 1b. Our analysis demonstrates that a higher chronicity rate of subtype 1b may be attributed to lower fitness constraints, enabling 1b viruses to more easily escape antibody responses. More generally, our results suggest that differences in evolutionary constraints between HCV subtypes may be an important factor in mediating distinct disease outcomes. Our analysis also identifies antibodies that appear to be escape-resistant against both subtypes 1a and 1b, providing directions for the design of HCV vaccines having cross-subtype protection.

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Section: Resultsmentioning

confidence: 99%

Evolutionary modelling of HCV subtypes provides rationale for their different disease outcomes

Zhang

McKay

2021

Preprint

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“…Our results showed that aa502-518-induced antisera can efficiently neutralize 3 HCV genotypes, TNcc(1a), S52(3a), and SA13(5a). In contrast, Czarnota et al recently reported that aa502-520 present on hepatitis B virus (HBV) small surface antigen virus-like particles could not induce neutralizing antibodies [ 38 ]. This discrepancy may be partially due to different immunogen coupling strategies; in our study, aa502-518 was conjugated to KLH protein.…”

Section: Discussionmentioning

confidence: 99%

Keyhole Limpet Hemocyanin-Conjugated Peptides from Hepatitis C Virus Glycoproteins Elicit Neutralizing Antibodies in BALB/c Mice

Deng

Chen

et al. 2021

Journal of Immunology Research

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Currently, no vaccine to prevent hepatitis C virus (HCV) infection is available. A major challenge in developing an HCV vaccine is the high diversity of HCV sequences. The purpose of immunization with viral glycoproteins is to induce a potent and long-lasting cellular and humoral immune response. However, this strategy only achieves limited protection, and antigen selection plays a crucial role in vaccine design. In this study, we investigated the humoral immune responses induced by intraperitoneal injection of keyhole limpet hemocyanin conjugated with 4 highly conserved peptides, including amino acids [aa]317-325 from E1 and aa418-429, aa502-518, and aa685-693 from E2, or 3 peptides from hypervariable region 1 (HVR1) of E2, including the N terminus of HVR1 (N-HVR1, aa384-396), C terminus of HVR1 (C-HVR1, aa397-410), and HVR1 in BALB/c mice. The neutralizing activity against HCV genotypes 1-6 was assessed using the cell culture HCV (HCVcc) system. The results showed that the 4 conserved peptides efficiently induced antibodies with potent neutralizing activity against 3 or 4 genotypes. Antibodies induced by aa685-693 conferred potent protection (>50%) against genotypes 2, 4, and 5. Peptide N-HVR1 elicited antibodies with the most potent neutralization activities against 3 HCV genotypes: TNcc(1a), S52(3a), and ED43(4a). These findings suggested that peptides within HCV glycoproteins could serve as potent immunogens for vaccine design and development.

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“…Moreover, we observed that few common exposed residues were associated with very high escape times for both subtypes (Figure S10). Interestingly, an epitope 412-425 comprising such residues (423 and 425) was shown in a recent study to be capable of inducing potent iScience Article neutralizing antibodies against multiple HCV genotypes including 1a and 1b (Czarnota et al, 2020). Hence, targeting these residues may assist in eliciting an effective immune response against both subtypes.…”

Section: Escape Time Comparison Indicates Subtype 1b May Evade Hmabs More Easily Than Subtype 1amentioning

confidence: 99%

Evolutionary modeling reveals enhanced mutational flexibility of HCV subtype 1b compared with 1a

Zhang

Quadeer²,

McKay³

2022

iScience

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Hepatitis C virus (HCV) is a leading cause of liver-associated disease and liver cancer. Of the major HCV subtypes, patients infected with subtype 1b have been associated with having a higher risk of developing chronic infection and hepatocellular carcinoma. However, underlying reasons for this increased disease severity remain unknown. Here, we provide an evolutionary rationale, based on a comparative study of fitness landscape and in-host evolutionary models of the E2 glycoprotein of HCV subtypes 1a and 1b. Our analysis demonstrates that a higher chronicity rate of 1b may be attributed to lower fitness constraints, enabling 1b viruses to more easily escape antibody responses. More generally, our results suggest that differences in evolutionary constraints between HCV subtypes may be an important factor in mediating distinct disease outcomes. Our analysis also identifies antibodies that appear escape-resistant against both subtypes 1a and 1b, providing directions for designing HCV vaccines having cross-subtype protection.Despite these observations, it remains unclear as to why subtype 1b infections may lead to more severe disease outcomes. This may be attributed to various reasons, including differences in viral phenotype, host-specific immune factors, demographics, transmission route (injectable drug use in the case of 1a

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Specific Antibodies Induced by Immunization with Hepatitis B Virus-Like Particles Carrying Hepatitis C Virus Envelope Glycoprotein 2 Epitopes Show Differential Neutralization Efficiency

Cited by 17 publications

References 68 publications

Evolutionary modelling of HCV subtypes provides rationale for their different disease outcomes

Evolutionary modelling of HCV subtypes provides rationale for their different disease outcomes

Keyhole Limpet Hemocyanin-Conjugated Peptides from Hepatitis C Virus Glycoproteins Elicit Neutralizing Antibodies in BALB/c Mice

Evolutionary modeling reveals enhanced mutational flexibility of HCV subtype 1b compared with 1a

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