Project number: LSHB-CT-2007-037435
Acronym: HEPACIVAC
Title: New preventative and therapeutic Hepatits C vaccines: from pre-clinical to phase 1
Summary:
The aim of the HEPACIVAC project is to develop efficacious prophylactic and therapeutic vaccines to Hepatitis C virus (HCV).
For this purpose, two vaccine companies in Europe, Okairos (a Biotech company created as a spin-off from Merck Inc.) and Novartis are joining their efforts with several European groups and one institution from Egypt.
To increase the probability of success, the ‘ideal HCV vaccine’ should be capable of eliciting both arms of the immune system, antibody and cellular responses.
Okairos, in collaboration with CeInge, has been working on a promising gene based HCV vaccine candidate using adenoviral vectors for delivery. This vaccine is based on the 2000 amino acid long HCV Non Structural region, elicits potent CD4+ and CD8+ T cell responses and works by eliminating infected cells, thus preventing chronic hepatitis.
A second vaccine candidate, previously developed by Novartis, consists of recombinant HCV glycoproteins, gpE1 and gpE2, associated to resemble a pre-virion envelope structure which is capable of inducing neutralizing antibodies. Both vaccine candidates have the potential to protect humans from a large number of HCV strains.
The goal of the HEPACIVAC project is to develop these two HCV vaccine components both at the pre-clinical level by testing safety, tolerability and immunogenicity, and at the clinical level by testing the two vaccines in healthy volunteers for safety and dose optimization and in chronically infected patients with and without the gold standard therapy.
The data obtained during the Project indicated that the Okairos NS vaccine has been produced in sufficient amount to conduct pre-clinical and clinical studies. At the pre-clinical level, the vaccine showed excellent immunogenicity in animals. The safety of the NS vaccine has been determined and the permission from Regulatory Authorities to use the vaccine for clinical trials has been obtained. The prophylactic clinical trial with this vaccine started on July 2008. The vaccine showed excellent safety and immunogenicity. The therapeutic clinical trial with the NS vaccine started on November 2009.
Production issues have delayed further testing of the Novartis vaccine in clinical trials. To overcome the production issues, also the gpE1 and gpE2 antigens are delivered using adenoviral vectors. However, it is unlikely to perform clinical trials with the adeno-based E1E2 vaccine in the timeframe of HEPACIVAC.
A back-up strategy has been designed. The alternative plan is to implement an expanded Phase 1 therapeutic vaccine trial with the NS vaccine.
All these studies will be performed with a strong commitment to translate the results into effective approaches for prevention and therapy of HCV, which represents the originality and uniqueness of the proposed project.
HEPACIVAC has the ambition of becoming a benchmark work for any other future HCV vaccine trial, using a comprehensive approach to standardise the pre-clinical and clinical trial procedures while taking further the development of promising HCV vaccines.
HEPACIVAC partners
The main characteristic of this Consortium is the presence of 2 vaccine companies in Europe: OKAIROS (a Biotech company created as a spin-off from Merck Inc.) and Novartis joined forces for the development of two of the most promising HCV vaccine so far available worldwide.
These two companies are flanked by important European partners for the basic research necessary to develop and standardize pre-clinical and clinical trials. In addition, in the HEPACIVAC project it is also involved one partner for the Mediterranean area, Egypt (listed in the FP6 INCO list), with strong interest and commitment to HCV prevention and therapy due to the very high prevalence of infection in Egypt.
The HEPACIVAC consortium is composed by twelve partners from seven countries. These participating groups have been carefully chosen for their technical expertise and scientific excellence. The most excellent scientists in the field of vaccine design and development will take part to this project. Some of them have already cooperated in many other projects within EU Programs and other initiatives, as showed also in the list of partner’s publications. On the whole, there is a high synergy among all participants which will guarantee the achievement of the project objectives.
All partners within the project have established groups, some of which of large size, with expert scientists and technicians and fully endowed with the facilities and instrumentation necessary for the project’s development. Partners will make available manpower and resources from their own groups to ensure the success of the project.
The HEPACIVAC strategy
The HEPACIVAC proposal aims at developing efficacious prophylactic and therapeutic vaccines to HCV.
Okairos developed a vaccine that elicits potent, broad and long-lived T cell immunity to eliminate infected cells and to prevent viral replication and spread, thereby leading to viral clearance. The vaccine candidate is gene-based, encodes for the 2000 amino acid-long HCV Non Structural region (from NS3 to NS5B) and utilizes adenoviral vectors for delivery. The data obtained during the first three years of the HEPACIVAC Project indicated that the OKAIROS NS vaccine has been produced in sufficient amount to conduct pre-clinical and clinical studies. At the pre-clinical level, the vaccine showed excellent immunogenicity in animals. The safety of the NS vaccine has been determined and the permission from Regulatory Authorities to use the vaccine for clinical trials has been obtained. A prophylactic clinical trial with this vaccine started on October 2008. The vaccine showed excellent safety and immunogenicity. A therapeutic clinical trial with the NS vaccine started on November 2009 on naïve patients.
Novartis developed a vaccine candidate consisting of recombinant HCV glycoproteins, gpE1 and gpE2, associated to resemble a pre-virion envelope structure. Antibodies elicited by this vaccine have a protective effect in animals against homologus and heterologous challenge.
Production issues have delayed further testing of the Novartis vaccine in clinical trials. To overcome the production issues, also the gpE1 and gpE2 antigens are delivered using adenoviral vectors. However, it is unlikely to perform clinical trials with the adeno-based E1E2 vaccine in the timeframe of HEPACIVAC. A back-up strategy has been designed. The alternative plan is to implement an expanded Phase 1 therapeutic vaccine trial with the NS vaccine. The patient population will be treatment relapsers (with the option to recruit non responders population) regardless of the previous therapy combinations.
Conclusions
The HEPACIVAC project will allow testing of two promising vaccines alone and in combination, performing pre-clinical studies and Phase I clinical trials:
- prophylactic, in healthy volunteers for safety and dose optimization;
- therapeutic, in chronically infected patients with and without anti-viral therapy.
Moreover, this project aims at standardising the procedures for pre-clinical and clinical trials for HCV vaccines, in order to avoid the problems occurred in the case of the HIV vaccines, for which the lack of standard procedures made the trials not comparable one to the other.
The ambitious but realistic goals of this unique project require the expertise, the optimal organization and the strong coordination that can only be provided by industrial settings like Novartis and OKAIROS, and the scientific know-how of the collaborators experience both in pre-clinical studies and in clinical trials. The expertise of these groups is expected to provide a correct exploitation of the newly acquired results of HEPACIVAC project.
CEINGE will lead the project and, together with OKAIROS and Novartis Vaccines&Diagnostics, will ensure an objective-oriented industrial approach and will guarantee the full exploitation of the achieved results. The industrial commitment offers unique opportunities from several points of view: (i) a professional coordination of the project (ii) the know-how and the infrastructures appropriate for implementing vaccine testing projects (iii) whenever necessary, guide and supervise activities so as to ensure the progression of the project towards the delivery of the objectives.
This project will also contribute to the training of young pre- and post-doctoral scientists in the diverse methodologies employed. The project will also lead the transfer of knowledge between participant groups from Europe and developing countries through direct meetings and through the exchange of young scientists.
Considering all these aspects, HEPACIVAC appears to respond perfectly to the scientific objective of the FP6 call.
News and further information about the project are available on the HEPACIVAC website http://www.altaweb.eu/hepacivac
Coordinator contact details
Riccardo Cortese
Via Comunale Margherita 482, 80145 Napoli
Phone +39.335.8104832
Fax +39.081.3737808
cortese@ceinge.unina.it
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