Broadly neutralizing antibodies against hepatitis C virus: location, location, location

Skinner, Nicole; Bailey, Justin R.

doi:10.1016/j.jhep.2020.01.005

Cited by 4 publications

(4 citation statements)

References 19 publications

(23 reference statements)

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“…Recent investigation on HCV vaccine adjuvants demonstrated that the induction of a strong T and B cell immunity is enhanced by choosing the right adjuvant[ 113 ]. The subject of vaccines producing neutralizing antibodies has also been briefly reviewed in two recent editorials[ 114 , 115 ].…”

Section: Can We Eradicate Hcv By 2030 With Daas Treatment?mentioning

confidence: 99%

Hepatitis C virus: A critical approach to who really needs treatment

Voumvouraki¹

2022

WJH

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Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.

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Section: Can We Eradicate Hcv By 2030 With Daas Treatment?mentioning

confidence: 99%

Hepatitis C virus: A critical approach to who really needs treatment

Voumvouraki¹

2022

WJH

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“…This construct induced nAbs in mice, but the response was still low. Further efforts are required to improve the immunogenicity of structurebased HCV epitopes, including incorporation to viruslike particles or nanoparticles [155]. Another important piece of information that is becoming available is a detailed picture of the human humoral immune response against HCV [86][87][88][89].…”

Section: Rational Immunogen Design For Antibody-based Vaccinesmentioning

confidence: 99%

“…Another important piece of information that is becoming available is a detailed picture of the human humoral immune response against HCV [86][87][88][89]. For example, it is now known that bnAbs in HCV-infected patients are predominantly induced by AR3/domain B and domain C of E2 [155], and specific combinations of these antibodies together with antibodies targeting the E1E2 complex (AR4) are associated with natural HCV clearance [98]. Thus, antigen design focused on eliciting antibodies against these regions should be considered in a potential vaccine.…”

Section: Rational Immunogen Design For Antibody-based Vaccinesmentioning

confidence: 99%

Hepatitis C virus vaccine design: focus on the humoral immune response

2020

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Despite the recent development of safe and highly effective direct-acting antivirals, hepatitis C virus (HCV) infection remains a significant health problem. In 2016, the World Health Organization set out to reduce the rate of new HCV infections by 90% by 2030. Still, global control of the virus does not seem to be achievable in the absence of an effective vaccine. Current approaches to the development of a vaccine against HCV include the production of recombinant proteins, synthetic peptides, DNA vaccines, virus-like particles, and viral vectors expressing various antigens. In this review, we focus on the development of vaccines targeting the humoral immune response against HCV based on the cumulative evidence supporting the important role of neutralizing antibodies in protection against HCV infection. The main targets of HCV-specific neutralizing antibodies are the glycoproteins E1 and E2. Recent advances in the knowledge of HCV glycoprotein structure and their epitopes, as well as the possibility of getting detailed information on the human antibody repertoire generated by the infection, will allow rational structure-based antigen design to target specific germline antibodies. Although obtaining a vaccine capable of inducing sterilizing immunity will be a difficult task, a vaccine that prevents chronic hepatitis C infections, a more realistic goal in the short term, would have a considerable health impact.

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“…Broadly cross-neutralizing antibodies target five antigenic regions (AR). AR1, AR2, and AR3 are located on the HCV envelope 2 (E2) protein, and AR4 and AR5 contain epitopes that have amino acids on both E1 and E2 proteins 30 , 31 . Such responses are also found in patients with established chronic HCV infection 26 , 32 , 33 , but they do not clear the autologous HCV strain, which has escaped via the selection of quasispecies with mutations that are not recognized 34 .…”

Section: Introductionmentioning

confidence: 99%

Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C

et al. 2022

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The increasing incidence of hepatitis C virus (HCV) infections underscores the need for an effective vaccine. Successful vaccines to other viruses generally depend on a long-lasting humoral response. However, data on the half-life of HCV-specific responses are lacking. Here we study archived sera and mononuclear cells that were prospectively collected up to 18 years after cure of chronic HCV infection to determine the role of HCV antigen in maintaining neutralizing antibody and B cell responses. We show that HCV-neutralizing activity decreases rapidly in potency and breadth after curative treatment. In contrast, HCV-specific memory B cells persist, and display a restored resting phenotype, normalized chemokine receptor expression and preserved ability to differentiate into antibody-secreting cells. The short half-life of HCV-neutralizing activity is consistent with a lack of long-lived plasma cells. The persistence of HCV-specific memory B cells and the reduced inflammation after cure provide an opportunity for vaccination to induce protective immunity against re-infection.

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Broadly neutralizing antibodies against hepatitis C virus: location, location, location

Cited by 4 publications

References 19 publications

Hepatitis C virus: A critical approach to who really needs treatment

Hepatitis C virus: A critical approach to who really needs treatment

Hepatitis C virus vaccine design: focus on the humoral immune response

Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C

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