PHARVAT (project completed)

Platform for the Harmonisation of Vaccine Adjuvant Testing

Background

PHARVAT aims to generate a harmonised procedure to permit pre-clinical selection of vaccine adjuvants throughout Europe. This will be based on:

  1. An in-depth survey and analysis of best practice currently being employed by members of AdjuNet, a network of adjuvant developers, users and researchers affiliated with the World Health Organization (WHO) Global Adjuvant Development Initiative (GADI);
  2. An evaluation of lead procedures in collaboration with TRANSVAC, a consortium of vaccine development infrastructure sites funded under FP7;
  3. A selection of one assay resulting from the TRANSVAC findings and validation by AdjuNet members;
  4. The dissemination of the harmonised assay by WHO through its web-sites and conferences.

Such tests will allow the activity / safety of adjuvants to be compared directly and will therefore constitute a major advantage in Poverty Related Diseases (PRD) vaccine development programmes.

In spite of the generation of important Science and Technology (S&T) information in many fields such as immunology, virology, molecular biology and microbiology/parasitology traditional methods of vaccine development have not produced effective vaccines for prevalent infectious diseases, including AIDS, malaria and tuberculosis. these difficult diseases call attention to the importance of new approaches emerging from modern technologies and to the costs of vaccines.

Successful efforts in vaccine design in the past have typically taken advantage of naturally occurring, protective immune responses provided by attenuated pathogens, but this approach is no longer applicable as new antigens arising from modern technology are used. Modern antigens are, at the same time, more specific, less dangerous and less immunogenic, but they also represent the major element of cost of modern vaccines. these are the reasons why most vaccine developers look for the most appropriate adjuvants, aiming to:

  1. Reduce the amount of antigen needed and
  2. Improve level and quality of the immune response while
  3. Not compromising the stability of the antigen and
  4. Doing no harm to the recipient.

It is a demanding set of requirements to provide stable, clinical grade products meeting these needs, but with recent advances in understanding of immune mechanisms a range of possibilities now exists for developing products that offer targeted stimulation of the immune system.

There are many organisations (private and public) that have entered into Research & Development (R&D) activities concerning new vaccines and/or adjuvants, in Europe and elsewhere. to date the search for innovative adjuvants has not been a priority in European Commission funded R&D policies and programmes, yet global efforts need to be better organised and there is an urgent need for harmonised testing and evaluation methods for selecting the most appropriate adjuvants.

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Objectives and Major Milestones

The overall strategy of the project is:

  • Surveying current best practice in global adjuvant R&D
  • Exploiting the expertise present in the participating organisations to analyse the survey results
  • Determining the tests that are the most appropriate for comparing adjuvant activities, and
  • Disseminating the results by a workshop, publication in scientific literature and websites.

This is achieved through four work packages:

WP1: Survey of best practice in global adjuvant R&D and database construction,

WP2: Evaluation of proposals for basic tests for adjuvants and approval by stakeholders,

WP3: Dissemination of the survey result, and

WP4: Management.

Conclusion

PHARVAT was bought to a successful conclusion in October 2011 with an adjuvant reference kit, which is available to the scientific community.

Three antigens were used, which can be obtained from Biomedical Primate Research Centre (AMA1), LIONEX (Ag85A), and World Health Organization (WHO) (HBsAg).  Sufficient high-titered antisera, which is in a repository at WHO, was generated for approx. 20,000 tests pr. antigen.  The three  reference adjuvants selected: Aluminium Oxy Hydroxide, Squalene Oil in Water (SWE),  and a liposomal formulation with the Saponin QS21, can be obtained from the Vaccine Formulation Laboratory (VFL) at the University of Lausanne.

A paper is being drafted, which will be published in a peer reviewed journal (a link will be created here when the paper has been published), which will constitute a reference for future adjuvant comparisons.

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