The War of Immunity

Vaccines are the most important breakthrough in modern medicine: the jewel in the crown of the pharma industry. What can the success of vaccines teach us about healthcare and the industry’s commercial model?

Out of the virus immunity comes.

Killing Joke’s lyric uses vaccines as a metaphor for the human ability to find a positive meaning in the darkest threat. The history of medicine has shown, time and again, that every disease holds the seeds of its own treatment – but to find the answer, you have to look deep inside the problem.

It has been said that no other health initiative, with the exception of clean drinking water, has done as much as vaccines to improve public health. Medical sales professionals love selling vaccines, for two reasons. Firstly, their potential to protect the young and the old against highly dangerous diseases is beyond reasonable doubt. Secondly, the sales model for vaccines is as dramatic as its medical impact: the supplier becomes responsible for securing the immunity of a population.

Yet, on the face of it, the public might wonder what the fuss is about. Vaccines are one-off medical treatments that protect against specific infections. Many are prophylactic: they don’t work if you have the disease. They are not 100% reliable, since pandemic infections have many competing strains. And they can have harmful side effects. So why should healthy people bother?

The answer lies in the list of deadly and disabling diseases that once cast a shadow over human life, but now are preventable: smallpox, polio, tuberculosis, measles, mumps, chickenpox, typhoid, cholera, bubonic plague, rabies, tetanus, diphtheria and pneumonia. For some viral infections, vaccines are the only effective treatment.

Vaccination programmes demand collaboration across disciplines and borders to protect populations and share medical innovations.  This collaboration model meets with scepticism on two sides: those who mistrust public health provision and those who mistrust the pharma industry. It’s not surprising, therefore, that vaccines meet with antagonistic campaigns and conspiracy theories from a coalition of unreason.

The body’s weapons

Vaccines are different from conventional medicines because they do not directly attack the disease: they provoke the body’s natural immune response against the disease, like a mock-invasion used as a military training exercise. A vaccine dose consists of dead or inactivated disease organisms, or biochemical agents derived from them. In designing a vaccine, scientists trade off risks and benefits.

The first vaccination was conducted by the rural English physician Edward Jenner in 1796. Hearing that local milkmaids who contracted a minor infection called cowpox never seemed to contract the deadly smallpox, he deliberately infected a farm lad with cowpox and then, when he had recovered, with smallpox. (Medical research ethics have improved somewhat since then.) The use of a live disease culture for immunisation is now called inoculation.

The first use of an artificial vaccine was conducted by Louis Pasteur in 1885, using a vaccine developed by his colleague Emile Roux by dessicating the spinal tissue of rabies-infected rabbits. Pasteur gave the vaccine to a boy who had been mauled by a rabid dog. He came to no harm.

Vaccines are still news, with global mobility and shifting demographics making the challenge of immunity more complex and urgent than before. In 2012, new vaccines were developed to treat meningitis, shingles, rotavirus (a cause of infant diarrhoea) and whooping cough. Vaccination against HPV, the cause of cervical cancer, is a new priority for health systems. The GAVI Alliance, dedicated to providing vaccination programmes for children in the developing world, has funding from the Bill & Melinda Gates Foundation and the support of many pharma companies.

A vaccine coalition

A leading company in the European vaccines field (and the only specialist firm) is Sanofi Pasteur MSD, a collaboration between two major pharma companies with a long history of investment in immunity. Sanofi Pasteur is founded on the work of the Pasteur Institute, while Merck’s Dr Maurice Hilleman developed vaccines for measles, mumps, hepatitis A and B, chickenpox, meningitis and pneumonia. The joint company protects half a billion European people against 20 major diseases.

Paul Hardiman, Communications Manager for Sanofi Pasteur MSD, told Pf about the company’s unique role in the European immunity landscape. There are three reasons for the collaboration, he explains: “It avoids a duplication of effort in the drive to develop new and innovative vaccines. It also allows a focus on the strengths and suitability of vaccines for different markets from both companies’ portfolios. This in turn gives flexibility and supports public health priorities.”

The two parent companies are both deeply involved in the global project of the GAVI Alliance. Both Sanofi Pasteur and MSD “use a policy of tiered pricing (linked to a country’s ability to pay) to enable access to vaccines in GAVI-eligible countries. This has included significantly reduced prices on vaccines against HPV and rotavirus and a pentavalent childhood vaccine against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type B.”

In the UK, Sanofi Pasteur MSD plays a major role in public health immunisation programmes for children, young adults and elderly people. These “are secured through competitive national tenders, requiring the consistent and timely supply of large volumes of high-quality vaccines”. The company has dedicated vaccine representatives selling directly to pharmacies and GP practices.

“Every year, the Joint Committee on Vaccination and Immunisation (JCVI) carries out a horizon scanning exercise to identify all potential new vaccines expected from manufacturers that may have an impact on public health over the following five years.”

As public health in the UK shifts to local authority provision, vaccine suppliers need to be fully aware of the economics and logistics of immunity. Sanofi Pasteur MSD’s UK sales force are “vaccine experts, engaging with practice nurses and GPs to support them in the areas of vaccine supply, campaign organisation and communication, and the education of vaccinating HCPs.”

The company is now supplying Gardasil for a schools-based vaccination programme to protect teenage girls against HPV and hence against cervical cancer. It is also preparing to supply Zostavax for a national programme, starting later this year, to immunise senior citizens against shingles. In the future, the company hopes to target, cancers, allergies, addictions and diseases of the central nervous system.

Immunisation programmes deliver savings both in the short term (by reducing the need for acute treatment) and in the long term (by reducing disability and chronic illness). As the focus of healthcare shifts further into the community, vaccines are increasingly crucial weapons in the HCP’s armoury. Their value, the company maintains, can be expressed in both health and economic terms.

Diplomatic immunity

In February 2013, nine female health workers responsible for delivering polio vaccination programmes in the Kano province of Kenya were murdered by gunmen after a local preacher condemned the vaccine as a plot to cause infertility. Similar killings have happened in Pakistan. In the US, ideologues opposed to public health programmes have accused the Obama government of spreading disease in order to experiment on the public with dangerous biological agents. The internet has given these conspiracy theorists a large audience.

In the UK, a spurious panic was created around the MMR vaccine by Andrew Wakefield’s article in The Lancet in 1998, which claimed the vaccine was a cause of autism. As the BMJ has recently reported, the article was scientifically discredited within a year, and has since been exposed as an “elaborate fraud” based on research that never took place. However, Wakefield’s claims are still declared to be accurate by the Daily Mail and its bizarre columnist Melanie Phillips.

Why do vaccines inspire so much mistrust? The reasons are complex. Some people believe that harnessing the body’s immune response is ‘interfering’ with nature. Others maintain that public health programmes violate the responsibility of the individual to determine their own healthcare. Still others claim that immunisation programmes are a form of covert surveillance, or even of biological warfare.

Paul Hardiman argues that vaccination may be a victim of its own success: “Anti-vaccine sentiment is thought to arise when people no longer fear the disease for which they are being encouraged to accept vaccination. As vaccine coverage increases, serious disease starts to disappear along with people’s fear of the disease. As people lose sight of the threat, so anti-vaccine sentiment may replace the good reasons for vaccinating – raising concerns in people’s minds.”

Doctor and writer Ben Goldacre, whose book Bad Science is strongly critical of anti-vaccine conspiracy theories, argues that the industry is not blameless: “I think it’s fair to say that anti-vaccine conspiracy theories are a kind of poetic response to the obvious regulatory failure in medicine and in the pharmaceutical industry. People know that there is something a little bit wrong here.”

For example, he notes, the recent murders in Nigeria took place in the same province where Pfizer had run the Trovan antibiotic trial in 1996 – a trial whose controversial nature led to Pfizer paying the Nigerian government £75 million to settle out of court, and inspired John le Carré’s novel The Constant Gardener.

Goldacre comments: “There’s something interesting happening when a very destructive anti-vaccine conspiracy theory built around fear and anxiety that drug companies are behaving badly arises in the same very small province in northern Nigeria where Pfizer have been running a trial which many regard as unethical.”