Product Profile - Engerix-B 74 Table
This article has been cited by other articles in PMC. Abstract Given the global prevalence and long-term complications of chronic hepatitis C virus HCV infection, HCV constitutes one of the greatest challenges to human health of this decade.
Considerable efforts have focused on the development of new effective treatments, but about three to four million individuals become infected each year, adding to the world reservoir of HCV infection.
The development of a prophylactic vaccine against hepatitis C virus has thus become an important medical priority. Only a few vaccine candidates have progressed to the clinical phase, and published data on both the efficacy and safety of these vaccines are limited, due to many scientific, logistic and bioethic challenges.
Fortunately, new innovative vaccine formulations, modes of vaccination and delivery technologies have been developed in recent years. Several preclinical trials of virus-like particle VLP -based vaccination strategies are currently underway and have already generated very promising results.
In this commentary, we consider the current state of prophylactic HCV vaccines, the hurdles to be overcome in the future and the various VLP-based vaccination approaches currently being developed.
This virus is thus a leading cause of liver transplantation in industrialized countries. Despite these considerable therapeutic advances, it is estimated that world reservoir of HCV-infected individuals is increased by three to four million newly infected subjects each year.
However, there are many obstacles to the development of vaccines against HCV, including the considerable sequence divergence of the HCV RNA genome, 9 leading to the emergence of mutants resistant to the humoral and cellular immune responses to infection, 10 - 12 and the limited availability of convenient small-animal models other than the chimpanzee, mimicking HCV infection in humans.
Conversely, there is encouraging evidence that it might be possible to develop a successful vaccine. In recent years, several different strategies, including the use of recombinant proteins, virus-like particles VLPsrecombinant nonpathogenic live vectors and prime-boost approaches, have been investigated for use in prophylactic vaccination against HCV, with various degrees of success.
However, several preclinical trials involving VLP-based vaccine candidates are currently underway and have already generated very promising results. A prophylactic vaccination strategy based on the use of adjuvanted recombinant E1 and E2 viral envelope proteins was, therefore, initially proposed.
This prophylactic vaccine effectively protected immunized chimpanzees against experimental intravenous challenge with the homologous 1a strain. Based on these encouraging data, a dose-ranging phase I trial was initiated to explore the safety and immunogenicity of this recombinant E1-E2 vaccine, which was found to be well tolerated and immunogenic in humans volunteers.
The coexpression of the full-length E1 and E2 genes has been shown to result in the synthesis of highly mannosylated immature glycoforms with a transmembrane domain TMD anchoring them in intracellular compartments in the form of a large, noncovalently linked heterodimer, making the extraction and purification of these proteins extremely difficult and essentially incompatible with industrial development for vaccination purposes.
However, such approaches have met with limited success, because the deletion of the TMD of these proteins has been shown to impair their antigenic and functional properties. This approach is justified by previous reports of convincing demonstrations of the efficacy of VLP-based vaccines, particularly for preventing persistent infection and associated diseases caused by hepatitis B virus HBV 46 and human papillomavirus.
The results of all these studies were encouraging, supporting the development of retrovirus-derived VLP-based vaccines, but the multiple-dose regimen required to induce a protective immune response nonetheless represents a major difficulty.
Moreover, the use of animal retroviral particles for the development of a prophylactic vaccine for humans will require validation, and the large-scale vaccine manufacturing process may represent a bottleneck for the development of vaccines of this type.
An alternative approach, overcoming the difficult production of such retrovirus-derived VLPs, involves the direct injection of DNA plasmids encoding proteins generating retrovirus-derived VLPs plasma-retroVLPs into mice. Virus-like particles constitute potential platforms able to carry full-length HCV E1-E2 envelope proteins in an appropriate conformation.
The generation of recombinant VLPs by fusing viral antigens of interest to heterologous viral structural proteins that can self-assemble into VLPs also constitutes a promising approach for the induction of HCV-specific immune responses. Many of the immunization assays conducted with such chimeric particles indicated that relatively weak antibody and T-cell responses to HCV epitopes were elicited, suggesting that the nature of the viral epitopes and the site of fusion are determinants of the process of protein assembly into VLPs and of the conformation and immunogenicity of the antigen.
The HBV S protein has been shown to self-assemble into highly immunogenic, noninfectious and secreted subviral particles, which have been used worldwide as a safe, commercial hepatitis B vaccine since the early s. However, the capacity of these chimeric proteins to self-assemble into VLPs and the induction of an effective immune response were not systematically demonstrated.
Further studies are required to increase the broadly neutralizing properties of the NAbs induced by this vaccination strategy, and to investigate this specific HCV-neutralizing response in different animal models, but the encouraging data generated by this study support the development of a bivalent HBV-HCV prophylactic vaccine candidate potentially able to prevent initial infection with either of these two hepatotropic viruses.
Such a vaccine would be of considerable value, because the populations at risk of infection with HBV and HCV through exposure to infected blood are essentially the same, in both developed and developing countries. Another major advantage of this approach is that this vaccine candidate could be produced by the same procedures established for HBV vaccines, reducing the time and cost of its industrial development.
In the last few years, many recombinant nonpathogenic live vector-based vaccination strategies have thus emerged. Despite the promising results obtained with this strategy, the adenoviral vectors were shown to suffer from the limitation that adenoviral infection is common in humans, and preexisting high-titer anti-vector NAbs may interfere with the immunological potency of such vaccines.
Attempts have been made to overcome this obstacle and to evaluate the safety and potency of such vaccines in healthy volunteers. Phase I clinical trials have been initiated to explore prime-boost immunization regimens involving the use of two adenoviral vectors based on rare serotypes expressing the HCV NS3-NS5B gene cassette.
Thus, HCV vaccine formulations comprising prime-boost heterologous immunization with a recombinant live virus-based vector seem to constitute promising approaches for eliciting strong cellular responses with broader ranges of epitopes, with the aim of clearing HCV infection.
As the resolution of HCV infection is frequently associated with the development of robust, cross-reactive and long-lasting cellular immunity and the production of NAbs, it would be very interesting to investigate, in a prime-boost regimen, a combination of the bivalent HBV-HCV prophylactic vaccine eliciting anti-E1 and anti-E2 cross-neutralizing antibodies with a vaccine inducing strong cellular immune responses.
The ultimate goal of these investigations would be the induction of highly protective, long-lasting immunity to HCV. In addition, the recently developed VLP-based strategies have already proved highly promising for the development of HCV vaccine candidates. All these encouraging data suggest that it should be possible to develop a prophylactic hepatitis C vaccine in the near future.Issuu is a digital publishing platform that makes it simple to publish magazines, catalogs, newspapers, books, and more online.
Pharmapoint prophylactic hepatitis b virus vaccines global drug. " A prophylactic hepatitis B vaccine with a novel adjuvant system Vaccine Mar 21;19() A prophylactic hepatitis B vaccine with a novel adjuvant system.
Thoelen S, De Clercq N, Tornieporth N Kline non-responding populations (e.g. non-responders, haemodialysis patients, elderly) who could benefit from a more immunogenic. Recently published research from GlobalData, "PharmaPoint: Prophylactic Hepatitis B Virus Vaccines - 5EU Drug Forecast and Market Analysis to ", is now available at Fast Market Research Boston.
PharmaPoint: Prophylactic Hepatitis B Virus Vaccines - US Drug Forecast and Market Analysis to Summary Hepatitis B, which is caused by the hepatitis B virus (HBV), is characterized by acute. Overview of Hepatitis B disease including epidemiology, etiology, symptoms, diagnosis, pathology and treatment guidelines as well as an overview on the competitive landscape.
PharmaPoint: Prophylactic Hepatitis B Virus Vaccines - 5EU Drug Forecast and Market Analysis to Summary Hepatitis B, which is caused by the hepatitis B virus (HBV), is characterized by acute.