Community Research and Development Information Service - CORDIS

FP7

HOOKVAC Report Summary

Project ID: 602843
Funded under: FP7-HEALTH
Country: Netherlands

Periodic Report Summary 2 - HOOKVAC (Developing and Testing a novel, low-cost, effective HOOKworm VACcine to Control Human Hookworm Infection in endemic countries)

Project Context and Objectives:
Approximately 600-700 million people are infected by hookworm, primarily in sub-Saharan Africa, Southeast Asia, and Latin America. Hookworm infection ranks number one in terms of Years Lost from Disability from a neglected infectious disease, and among the top 3 in terms of lost Disability-Adjusted Life Years. HOOKVAC is developing the first and only vaccine for human hookworm infection. A bivalent, low-cost vaccine candidate will be clinically tested for the first time in an African disease endemic population. This is done in Gabon in a very typical setting within the Central African rainforest belt, where the incidence of hookworm infections is 30%. Cost effectiveness modelling has shown that such a vaccine will significantly improve the efficacy of the current mass drug administration programs. HOOKVAC plays a crucial role in advancing toward large scale efficacy studies in African endemic areas. Via a program of 48 months with 6 work packages, HOOKVAC addresses 4 main objectives: (1) establish safety and immunogenicity of the vaccine candidate in an endemic population (2) improve the manufacturing process (3) provide clinical proof of concept (4) improve accessibility of the vaccine in endemic areas.

Project Results:
WP2: All study related visits for HV001 have been completed, with the final visit of the last participant completed mid-August 2016. The last batch of serum samples have been shipped to George Washington University on 2 November 2016, where the final immunology assessments are done. An interim safety report for data up to day 208 has been made (see the supplement “Day 208 Interim Safety Report”). The vaccine was found to be well tolerated and safe, with no vaccine-related Serious Adverse Events.
Two presentations were given on the interim results of the HV-01 study
1. Oral presentation at the Eight EDCTP Forum (Lusaka, Zambia), 9 November 2016. By Dr. Ayola Akim Adegnika: Safety and Immunogenicity of Co-administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 with Alhydrogel® and Glucopyranosyl-Lipid A in Gabonese adults
2. Poster presentation at the ASTMH 65th Annual Meeting, 14 November 2016 (Atlanta, USA). By Dr. Ayola Akim Adegnika: Safety and Immunogenicity of Co-administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 with Alhydrogel® and Glucopyranosyl-Lipid A in Gabonese adults
Currently, the final data is being cleaned and prepared for analysis, the expected date for the first draft for the final scientific publication is July 2017.
Preparations for studies HV02 and HV03 have started, and ethical/regulatory approvals have been obtained (HV02) or are being obtained (HV03)
WP3: For GST-1, an engineering run has been performed under cGMP-conditions according to the developed fermentation and production process described in the periodic report 1. The fermentation was performed on 40 liter scale. Na-APR-1 has previously been produced as a recombinant His-tagged protein with ER retention signal (KDEL) in tobacco plants, the according expression levels are very low. Only milligram quantities have been obtained out of kilograms of plant extracts. One of the major problems is the tendency of the protein to form aggregates. For further use as an injectable, it is recommended to produce the Na-APR-1 protein without His-tag. In this reporting period, we have expressed The m-APR-1 in a E. coli GI724 strain as alternative production platform. The overall yield of M-APR is over 30 mg per liter fermentation equivalent. The purified product has been shipped to Sabin for biochemical analysis and for immunogenicity study. Stability study of the purified M-APR is ongoing.
WP4: The results obtained after the evaluation of stability have shown that the co-formulation of Na-APR-1 and Na-GST-1 using the backbone of each current buffer formulation is not feasible. The presence of Empigen BB in the buffer impairs the ability of incorporating other molecules such as GST to the mix. We have learned from these results that to in order to develop a stable bivalent vaccine alternative excipients must be identified and screened.
WP5: Assessment of serum responses to vaccination indicate that both vaccine candidates are immunogenic and that high dose is needed for induction of a strong antibody response (with the currently used GLA adjuvant, this may be different for different antigens).
WP6: We have developed an updated Global Access strategy for the Human Hookworm Vaccine. Through the HOOKVAC consortium it has been advanced through meetings with the World Health Organization (WHO). Partners of the HOOKVAC consortium have started exploring manufacturing of the hookworm vaccine in India through a EuropeAID EC-India innovation program. A landscape analysis of Indian vaccine manufacturers was carried out. Additional conversations have taken place at meetings of the Developing Countries Vaccine Manufacturers Network. Advocacy efforts have focussed in promotion of NTD R&D (especially the hookworm vaccine), encouraging further investment by key country governments including Germany, Japan, Netherlands, Norway, United Kingdom and the United States, and with the EC. Advocacy activities have included policy briefs and pamphlets, events and one-on-one meetings.

Potential Impact:
HOOKVAC is specifically designed to take relevant steps needed to ensure a strong impact: 1) Eliminating hookworm infection as a major public problem by developing a vaccine with at least 80% efficacy against moderate and heavy hookworm infections that lasts at five years after immunization, 2) Transfer of gained knowledge and expertise during the development of the hookworm vaccine from Sabin PDP partners to HOOKVAC consortium partners; 3) Perform clinical Phase I trials in adults and children in an endemic African population to provide safety and immunogenicity data of the co-administered hookworm antigens; 4) Optimise manufacturing process for Na-GST-1 and Na-APR-1 to improve yield and lower the cost of the vaccine; 5) Improve ease of administration and mode of action by incorporating both the Na-GST-1 and Na- APR-1 in a co-formulated bivalent vaccine together with an adjuvant; 6) Perform clinical Phase I/II trial in adults in an endemic African population to evaluate safety, immunogenicity and efficacy of the bivalent hookworm vaccine; 7) Involve advocacy and policy leaders to ensure dissemination of project results. These impacts will be achieved through: 1) A multidisciplinary consortium of worldwide experts in pre-clinical and clinical development, co-formulation strategies, process development, cGMP manufacturing and immunology; 2) Building upon research done by PDP partners within a larger 12 year development program of the human hookworm vaccine; 3) Involving knowledge of end-user communities and health professionals; 4) Active engagement with advocacy and policy leaders. Taken together, all these elements in the HOOKVAC program are expected to ensure advancements in developing a new, safe and efficacious vaccine to combat hookworm. Currently discussions on developing a business case for financing post project vaccine development are ongoing – these discussion are modelled on the recent business case for the Global TB Vaccine Partnership that was developed with help of KPMG and EIB

List of Websites:
www.hookvac.eu

Contact

Friso JANSSEN, (Manager Contracts)
Tel.: +31 20 5667800
E-mail

Subjects

Life Sciences
Record Number: 196962 / Last updated on: 2017-04-13
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