In the third paper of the Series, Professor Jeffrey W Almond and Dr Jon Smith, Sanofi Pasteur, Marcy L'Etoile, France, and Professor Marc Lipsitch, Harvard School of Public Health, Boston, MA, USA, look at the range of factors that influencing vaccine production, access, and uptake, and focus on the H1N1 influenza pandemic to exemplify the challenges of vaccine development on a global scale.
The technologies used to manufacture different types of vaccines affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. For example, oral polio vaccine strains grow well in culture, allowing production of hundreds of millions of doses at low cost; this has been the cornerstone of WHO's polio eradication campaign. By contrast, multivalent pneumococcus and human papillomavirus (HPV) vaccines have more complex production methods, requiring higher investment resulting in higher costs. Different national regulations, shelf life, and cold chain requirements are among the other factors affecting vaccine cost.
In most countries, a primary series of vaccinations for infants is well established and the vaccines included are readily available, although the precise schedules vary. In developing countries, vaccine uptake and access have been significantly improved in the past decade by the launch of the GAVI Alliance. The 72 countries that qualify for GAVI assistance are home to about half the world's population. The more complex vaccines are less available in developing countries. One reason is vaccine manufacturers need to recoup investment (up to US$1 billion for a new vaccine) by prioritisation of supply to markets that can sustain a high price.
The authors highlight the example of influenza vaccine to illustrate the issues around vaccine production and distribution. The egg-based manufacturing system has been reliably supplying seasonal influenza vaccine for several decades. But the authors note that this system has clear timing and capacity constraints and, following the recent H1N1 influenza pandemic, a perception has arisen that it needs to be updated. In future, new technologies such as cell culture or recombinant DNA methods could be used to express viral proteins in, for example, insect cells, tobacco plants, or fungi. Such technologies, once fully developed, are potentially better able to respond to global demand during a pandemic, but the authors conclude that the path ahead for these technologies is not straightforward and egg-based production will be the mainstay of supply for many years to come. Another issue is the lack of so-called 'surge' capacity within the vaccine industry (the ability to rapidly scale-up production in a pandemic). One suggestion is to have a warm-base facility, funded partly by governments, that could rapidly spring into action if needed in a global emergency. But such a model would be complex to maintain as highly trained staff would need to be available to run this facility and sufficient raw materials would be needed at short notice.
The authors conclude: "The response of global industry is not yet sufficient to meet the full need for pandemic influenza vaccine in a timely and equitable manner and, even with improvements, vaccine will need to be used wisely to achieve maximum protection."
Professor Jeffrey W Almond, Sanofi Pasteur, Marcy L'Etoile, France. Please contact via e-mail to arrange interview. T) +33 437379453 E) jeffrey.almond@sanofipasteur.com
Professor Marc Lipsitch, Harvard School of Public Health, Boston, MA, USA. Contact via e-mail. E) mlipsitc@hsph.harvard.edu
Journal
The Lancet