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

ABSTRACT: 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.

SUBMITTER: Sepulveda-Crespo D

PROVIDER: S-EPMC7338099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is conflicting evidence about whether a double dose of the hepatitis B virus (HBV) vaccine induces better immunity than the standard-dose vaccine for people living with HIV (PLWH). This study provides a meta-analysis that summarizes the efficacy of HBV vaccine regimens among HIV-infected patients, clarifying the role of particular factors such as dose and frequency of vaccination in vaccine responsiveness and highlighting the need for evidence-based practice to assess HBV vaccination among PLWH.MethodsRandomized clinical trials (RCTs) and prospective studies reporting vaccination response rates among PLWH were found through a search of PubMed, Cochrane, and the Web of Science. The key outcome was vaccine response. A random-effects model was used to estimate the pooled response rate. Subgroup analysis was conducted to evaluate key factors and explore sources of heterogeneity. Possible biases were assessed using quality and publication bias assessment.ResultsEligible studies included controlled trials that examined the effects of 17 interventional studies with 1,821 participants. Among PLWH who received the HBV vaccine, the pooled response rate of HBV vaccination was 71.5% (95% CI 64.0%-77.9%, p < 0.001). Compared with the standard dose (65.5%, 95% CI 53.1%-76.1%), the double dose (75.2%, 95% CI 66.2%-82.5%) was associated with a better response rate [Q(1) = 19.617, p < 0.001]. When stratified by schedule, the four-dose schedule (89.7%, 95% CI 83.1%-93.9%) had a higher response rate than the three-dose schedule (63.3%, 95% CI 56.6%-69.4%) and the difference was significant [Q(1) = 88.305, p < 0.001]. PLWH with higher CD4+ T-cell counts (>500 cells/mm3) at the time of vaccination had better response rates [Q(1) = 88.305, p < 0.001].ConclusionsIn this meta-analysis, the double dose of the HBV vaccine and multiple injections were associated with better immune responses than the standard HBV vaccine regimen in PLWH. Higher seroconversion rates were observed in PLWH with high CD4+ T-cell levels, indicating that individuals infected with HIV should receive the HBV vaccine as soon as possible after diagnosis.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

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

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