Vaccines are arguably one of the most successful public health tools for reducing disease and saving lives across the world. This is not new, but attending the World Vaccines Congress in Lyon was a reminder that the story of vaccines is far from over. Everything in vaccines is changing: the locus for R&D and manufacturing, the market, the regulatory framework, and the technology itself. All of which impact vaccine supply, cost and effectiveness in developing countries.
The story of emerging markets are becoming important. Early success stories were revisited such as the Serum Institute of India’s acquisition of Dutch national vaccine manufacturing capability. The story continued with the report by Dr Jan Hendrick (RIVM) that technology transfer agreements have resulted in the relocation of vaccine projects to the Serum Institute and a lowering of vaccine prices due to the lower cost of manufacturing and scaling up vaccine products. Emerging countries were talked about as being on a ‘self sufficiency mission’. Interestingly over 50% of doses for Brazil’s national immunisation programme in 2010 were provided by public manufacturers. Will emerging country manufacturing capacity impact vaccine price in developed countries? The quality of vaccines were reported as good enough to meet European standards, but regulatory requirements are increasingly demanding, and so the regulatory environment may prove to be the dominant deciding factor in the future.
Improvements in technology showed massive potential to improve vaccine delivery and effectiveness in developing countries. Future plans to accelerate the polio eradication project included antigen sparing through the use of new adjuvants, needle free vaccines and cold chain independent vaccines. Bioneedles have been in development for a few years now and involve a tiny needle-like device made of biodegradable polymers that are shot into the skin. There was much discussion of new vaccine targets, novel adjuvants and new enabling technologies.
There were discussions of new platforms, which I interpreted as associated and transferable sets of technologies and knowledge bases which can be used to launch new vaccines. Platforms are being developed rather than knowledge which centres around individual vaccines. There are for example viral platform technologies, bacterial platform technologies (including conjugate technologies) and unusually discussion featured a nanoparticle platform. The talk by Peter Keller from Selecta biosciences illustrated the work that had been done using nanoparticle polymers to create a synthetic vaccine. A synthetic vaccine that is not a biological, yet works in the same way as a vaccine. Selecta biosciences is based in the emerging market of Russia and has in development (approaching the pre-clinical stage) a vaccine candidate for malaria.
While history shows a technology push innovation generally in vaccines, which is still happening through these enabling platforms, GAVI intends to shape markets by providing pull mechanisms. One mechanism is to create advanced market commitments. Theoretically this creates a market, increases supply capacity and reduced price through competition. However, whether this actually happens proved to be a subject of some contention. One set of studies on pneumococcal vaccines shows that there is no evidence the pull mechanism is creating any of these benefits.
The challenges of conducting clinical trials are ongoing. They include mistrust, difficulty in recruitment, corruption, political instability, high turnover of trial site staff, cultural differences, lack of translation and the lack of appropriate expertise. PATH is dedicating effort to build standard vaccine trial sites with infrastructure and supporting services, staff training in finances, advocacy, standard operating procedures, crisis communication etc. It was reported that to solve some of the problems would additionally require community engagement plans and of community and national advisory boards (which will not come as a surprise to DPP researchers who have undertaken extensive study of clinical trial sites in Africa. See M.Upton, 2011).
Also not new to DPP was the discussion of ‘new’ partnership models including PDPs (see Chataway et al, 2008). Though what is new, is the progress being made in vaccine products that is a result of these partnerships. Merck in collaboration with NIH has resulted in the only recombinant sub-unit vaccine candidate for dengue, currently in phase 1 trials. Compared with live attenuated vaccines, the recombinant sub-unit vaccine has a shorter dosing response and reduced risks associated with precursor membrane protein (prM) antibodies (which are thought to assist the virus in infecting more cells).
Importantly the Vaccine Congress also took a look ahead at systems of vaccine delivery and the potential for vaccine shortages. The vaccine supply system architecture was set up in the 1980’s by the WHO. It is a simple multi-level system that follows each countries administrative organisation. Vaccines are ‘pushed down’ and the information required for re-ordering is ‘pushed up’. It’s a system that has worked well though does have redundancy with vaccines being kept in stock and often there is wastage as vaccines expire. This system was built around routine immunisation (e.g. tetanus). In the 2000’s, there has been increasing support for immunisation campaigns (e.g. Meningitis A, Polio). Campaigns and the Expanded Program for Immunisation have increased the pressure on vaccine delivery systems – they just cannot cope with the massive amount of vaccine that need to be delivered. A presentation by the WHO showcased the Optimize program (http://www.path.org/projects/project-optimize.php), which aims to update the system architecture in line with the most recent advances in vaccine science. For example, the usual storage conditions are labelled as standard: 2 -8 degrees. However, better vaccine design can result in better heat stability (e.g. lyopholized vaccines, though there are more steps involved in reconstituting these vaccines, and therefore greater risks). In fact I met a biotech company representative which works in improving heat stability of vaccines. Other studies show that even current vaccines can be stored and administered at higher temperatures and so a relatively simple solution would be to allow a licence and the vaccine label to reflect the true heat stability of the vaccine.