Innovative adjuvanted influenza vaccines: a Swiss-Indonesian collaboration towards better pandemic influenza preparedness

Two main types of inactivated influenza vaccines are currently available: whole inactived virus (WIV) vaccines (based on whole virus particles) and split vaccines (based on fragmented parts of virus particles). In comparison to split vaccines, WIV vaccines are less expensive to produce and benefit from a simpler method of production. Pre-pandemic vaccines, i.e. vaccines designed and produced before an influenza pandemic occurs, are usually of limited efficacy against new pandemic influenza strains, whose surface antigens are novel and are evolving continually over time as the virus circulates. Therefore, a specific pandemic vaccine needs to be developed and produced in a real-time situation. Because of this, the number of available doses of such a pandemic vaccine will likely not be enough to cover the global needs in a severe pandemic situation, especially in countries where local manufacturing capacity is limited. One approach to overcome this likely shortage is the inclusion of adjuvant technologies in the vaccines. Adjuvants can potentially: i) decrease significantly the amount of vaccine antigen required per dose, ii) decrease the number of doses required per person, iii) allow pre-pandemic vaccines to be more effective against novel pandemic strains.

Adjuvants such as oil-in-water emulsions (OiW) have previously been demonstrated to be compatible with split influenza vaccines. However, little is known about their compatibility and their potential with WIV. This project aims to develop new approaches that could induce protection against pandemic influenza using a single-dose WIV vaccine, as well as accelerating the timeframe for vaccine preparation and reducing significantly the costs of pandemic influenza immunization (through the use of less vaccine antigens per dose). This project will explore different formulation strategies: 1) the potential of WIV as a single-shot vaccine when combined with adjuvants; 2) the potential of new polymer microsphere formulations as influenza vaccine candidates; 3) the potential of co-injection of a free WIV and a microsphere-entrapped WIV, both being of different clades/strains.

Vaccine formulations will first be developed and characterized by the Swiss partners. In a second step the appropriate technologies will be transferred to the Indonesian partner and tested in mouse and ferret models.

This projects aims to develop a new generation of effective influenza vaccine candidates which could easily be produced by Indonesian vaccine manufacturers. In parallel, the project aims to set up a unique “Indonesian vaccine formulation platform”, involving the equipment, protocols, materials, and know-how acquired and developed in this project. This platform will aim to provide access to various adjuvants and formulation technologies for the Indonesian and the global scientific communities, will help to bring together a network of adjuvant providers and users, and will allow local stakeholders to develop new collaborations for testing their vaccine candidates with a variety of modern adjuvant systems. Most importantly, the application of this technology to influenza WIV vaccines will open up new perspectives in terms of Indonesian pandemic preparedness.

• Indonesia. Indonesia is a country particularly vulnerable to pandemic influenza. The highly pathogenic H5N1 influenza virus was first isolated in Western Java in 2005, and would later become responsible for more than 100 deaths, with an extremely high mortality rate (>80%) in humans. As of today 32 out of the 33 provinces in Indonesia have enzootic H5N1 in birds and other animals. Should H5N1 become widely transmissible to humans, it would quickly represent a grave threat to the population of Indonesia, and eventually to all of humanity. Although vaccination against influenza represents an essential public health tool for prevention, local production of influenza vaccine and access to vaccine adjuvant technologies are still limited in many developing countries, including Indonesia. This project aims to advance new and innovative vaccine technologies in order to improve access to pandemic vaccines in countries like Indonesia, therefore promoting better local, regional and global pandemic preparedness

• Link to project on SNSF research database P3