AN INDEPENDENT SUPPLEMENT FROM MEDIAPLANET ABOUT VACCINES, DISTRIBUTED IN THE TIMES

VACCINES12 MARCH 2007 AN INSIDE LOOK AT THE LATEST IN VACCINE RESEARCH AND DEVELOPMENT

A healthy, happy tomorrowis every parent’s mission.

It’s ours, too.ADVANCING SCIENCE FOR BETTER HEALTH

www.medimmune.com

AN INDEPENDENT SUPPLEMENT FROM MEDIAPLANET ABOUT VACCINES, DISTRIBUTED IN THE TIMES2

CONTENTS

Two candidates enter testing in the race to find a vaccine for Hepatitis C p. 4

If bird flu strikes p. 4

Tomorrow’s vaccines promise quick and easy treatments p. 5

Why global access to vaccines is a life and death issue for many p. 7

Vigilance the key to keeping vaccines safe p. 8

Complacency - the enemy that allows disease to sneak back p. 8

Influenza p. 9

New energy into the vaccine market p.10

Revolutionising protection against two major diseases p.11

www.mediaplanetgroup.co.uk

VACCINES, A TITLE FROM MEDIAPLANET

Project Manager Kerren Triffon, Production Editor UlrikaFallenius, Editor Tom Rowland, Design Sophie Wester-berg, Prepress Jez MacBean, Print News InternationalFor more information about supplements in the daily press,please contact Carl-Philip Thunström 020 7563 8877

Mediaplanet is the leading European publisher in providing high quality and in-depth analysis on topicalindustry and market issues, in print, online and broadcast.

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After years of being regarded as the Cinderellas of the pharmaceuticalbusiness, vaccines have been reinvented as the 21st Century wonderdrugs. More than 11 million people die every year from infectious dis-eases - one person every 3 seconds. A quarter of these deaths are causedby diseases that can or soon will be preventable using vaccines. A further8 million people also die each year from diseases for which effective vac-cines are not yet available, making this an ever-expanding market. Fol-lowing several years as the poor relation of the pharmaceutical industry,vaccines are once again being seen to be the most effective interventionagainst these infectious diseases as well as other emerging threats suchas bio-terrorism and Avian Flu.

So it comes as no surprise to find that industry, organisations and gov-ernments have renewed their commitment to vaccines. Driven by theapproval of new and improved combination vaccines and technologicalinnovations, the vaccine industry has re-emerged as a vibrant force inthe global pharmaceutical market. With the promise of new vaccinesemerging as alternatives to prevent or mitigate a wider portfolio of dis-ease, the resurgence looks set to continue.

The industry is undergoing major change and delivering healthygrowth in the process. Globally, the vaccine market is valued at morethan £5 billion ($10 billion), but as new vaccines are made available, thesize of the market is expected to exceed £7 billion ($15 billion) by 2012.

Paediatric vaccines have long dominated the market, yet it is the num-ber of available adult vaccines that is increasing at a faster rate, bolsteredby strong influenza and hepatitis sales and the early promise of cancervaccine development.

The pace of vaccine development has accelerated dramatically overthe last 20 years and manufacturers are researching and developing newvaccines using their knowledge of DNA technology and immunotherapy.

Some things however, never change. The demand, indeed the need, forwidespread vaccination at an affordable price in the developing worldcontinues unabated. Many life-threatening diseases still have no vac-cine associated with them. This significant fact illustrates the duality of amarket where growth has been due to revenues from North America andEurope. In the developed world spectacularly successful immunisationprogrammes have been put at risk as populations turn away from vacci-nation and memories of the horrors of the original disease fade. On page8 we look at the re-emergence of diseases, which a few years ago looked

to be in headlong retreat. Without a united effort by rich countries, rapidaccess to life-saving vaccines will remain a dream in many poorer partsof the world. Cervical cancer is now the second most common canceramong women and 80 per cent of deaths resulting from this cancer occurin the developing world where access to screening and treatment isextremely limited. A number of pharmaceutical companies remain theR&D powerhouses that pump new energy into the vaccine market. Thereare six key players among the pharmaceutical companies engaged in theresearch and development of ground-breaking new vaccines for theinternational market. Their work has dramatic implications for the quali-ty of life for millions of people. Creating a credible and effective vaccinesafety system will become even more important in the future. Since fewvaccine preventable diseases are eradicable, most immunisations willcontinue indefinitely and obtaining accurate data on and developingmethods to minimise the risks from the vaccines will be essential tomaintaining public acceptance of vaccinations.

Having said that, currently research and development for neglecteddiseases occurs primarily through public-private partnerships. NGOssuch as the Bill and Melinda Gates Foundation and the GAVI Alliancelead the way in philanthropic funding measures but the issue of vaccinedevelopment and usage in developing countries must be addressed bythe global health community. At the moment pharmaceutical andbiotechnology companies have little incentive to develop vaccines fordeveloping regions. Markets are small and risky and vaccine demand canbe unpredictable. Increasing the value proposition for companies to pur-sue developing world diseases remains a key driver to boosting privatesector involvement.

“We must continue to conduct research and development that equalsor exceeds international standards, and we must continually employ newtechnology to produce the best possible vaccines to improve humanhealth worldwide”, said Dr Lance Gordon, former President and ChiefExecutive Officer of VaxGen.

Presenting innovative approaches to tackle global vaccine challengesis a position that the World Vaccine Congress Washington aims to pro-mote in its 7th annual congress from 19-22 March. It will examine howthe global health community is adapting their roles and strategies to sat-isfy tomorrow’s vaccine issues, today.

For further details see www.lifescienceworld.com/2007/WVC_DC

The World Vaccine Congress Washington will explore many of the tough issues in the vaccine communitytoday and will present innovative approaches across the public and private sectors that are being suc-cessfully deployed. For more information on this groundbreaking event contact Julie Phillips, tel +44 (0) 207 539 4336 or e-mail julie.phillips@terrapinn.com

From old hat to new hope for the future

Novartis Vaccines and Diagnostics

For all the right reasons…In pursuing our mission to treat patients, prevent disease, ease suffering and

enhance the quality of life around the globe, Novartis is proud to build upon

the scientific expertise of Chiron. We will focus on furthering critical research

while working to ensure a strong supply line that can reliably provide vaccines

and diagnostics worldwide.

www.novartis.com

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If bird flu strikes where will we getthe eggs used to grow the vaccine?Vaccine companies, including Solvay and MedImmune, are pioneering new manufac-turing techniques to fight the menace of a bird flu pandemic.

Further, a severe outbreak of avianinfluenza could kill the flocks usedto produce the eggs used for vaccineproduction. It was recorded in 2003that nine rich countries including theUnited States, used 62 per cent of theworld’s influenza vaccine leavinglittle for those poorer countrieswhere bird flu is most rampant.

In the event of a pandemic billionsof doses would be needed and cur-rently it would be very difficult tostep up global vaccine production tomake the amount required. To tackleinfluenza A (H5N1), researchers havealready used reverse genetics to cre-ate candidate vaccines capable ofstanding up to this virus. Reversegenetics is a method by which virus-es such as influenza can be generat-ed entirely from segments of DNA.

Solvay Pharmaceuticals has, usingthis reverse genetics technique,invested more than 50 million Eurosin a new facility in the Netherlands,for the production of influenza vac-cines generated through their cellculture method: Influvac®TC. Addi-tionally, Solvay has been awarded a$298 million grant to support build-ing a similar facility in the US to aidpandemic preparedness.

With their MDCK cell culture-based manufacturing technologythey are replacing the traditionalegg-method and instead developingmethods where the virus is grownin huge metal fermenters contain-

“The H5N1 strain of avian flu couldinfect up to 20 per cent of the world’spopulation, if a human pandemicstrain emerges,” said Albert Oster-haus, the Dutch influenza expert.

Vaccines, which match the pre-dominant circulating strains, havebeen reported to be the most impor-tant medical intervention for pre-venting flu and to reduce theimpact of pandemic flu on the pop-ulation. Vaccine companies cur-rently make approximately 300 mil-lion flu shots a year, worldwide.Current vaccines used by the major-ity of the world consist of inactivat-ed influenza virus. They aim toinduce immunity by producinghaemagglutination inhibition orneutralising antibodies.

The vaccine is produced in fer-tilised hens’ eggs, using “highgrowth” strains and, after purifica-tion and quality testing, is supplied todoctors in pre-filled syringes foradministration by intramuscularinjection.

Current production cycles aredesigned to release the vaccine intime for annual vaccination cam-paigns. These take place before thewinter season starts. However, expe-rience shows that a pandemic virusdoes not follow normal seasonalrules. Vast quantities of the vaccineare hard to produce quickly and prob-lems with supply could occur in theevent of a pandemic.

ing a soup of cultured cells whichwould enable them to scale up andkeep pace with evolving influenzaviruses.

Once the virus strain has beenidentified the cell culture process hasthe potential to reduce the start-uptime for manufacturing from fourweeks to two or three weeks.

This method offers a number ofother benefits. Vaccine manufactur-ers can bypass the step needed toadapt the virus strains to grow ineggs and as a result they may beoffered to people who are allergic toeggs and therefore unable to receivethe current vaccines. Cells may alsobe frozen in advance and large vol-umes grown quickly to meet surgingneeds in the event of a pandemic.

In the US MedImmune is currentlymarketing influenza vaccine, Flu-Mist®, which is made using chickeneggs. It is currently available forhealthy children and adolescentsaged five to 17 and healthy adultsaged 18 to 49. Rather than injectingthe vaccine, it is administered via anasal mist. Research of the compa-ny’s pivotal phase 3 clinical trialsusing a new refrigerated formula-tion was published in February’sissue of the New England Journal ofMedicine.

The study of 8,400 children agedsix months to 59 months showed 55percent fewer flu cases among thegroup who received the nasal spray

flu vaccine compared to the groupwho received the injectable flu vac-cine. Based on the results of thisstudy MedImmune is seekingapproval from the US Food andDrugs Administration to make Flu-Mist available for children as youngas one year of age who do not have ahistory of wheezing or asthma. Thecompany is also turning to usingstate-of-the-art cell culture methodsto produce influenza vaccines with-out the need of chicken eggs. InDecember 2006 they licensed theirproprietary reverse genetics intellec-tual property to CSL of Australia to

support the development of theirnew generation of vaccines.

MedImmune is collaborating witha number of entities to explore vac-cine development techniques thatcould be used in the event of a pan-demic flu outbreak. The US NationalInstitutes of Health (NIH) beganenrolling participants in a Phase 1study of an intranasal H5N1 influen-za vaccine candidate based on Med-Immune’s live, attenuated vaccinetechnology, using reverse geneticstechnology. Researchers at MedIm-mune and Johns Hopkins BloombergSchool of Public Health Center forImmunization Research, where thestudy is being conducted, are hope-ful that a live, attenuated intranasalinfluenza vaccine would be as effec-tive against potential pandemic Astrains as it has been shown to beagainst seasonal matched and mis-matched A strains of influenza.

British Immunisation scheduleAll children in the UK are offered vaccinations against key diseases as partof the national childhood immunisation schedule. The most recent changesin September 2006 have seen changes to the meningitis C schedule withonly two doses, not three given in the first four months, also there has beenthe addition of a booster dose of meningitis C/Hib vaccine at 12 monthsand the addition of the pneumococcal vaccine, which protects against atype of bacteria that can cause meningitis and other serious infections.

Usually, the pneumococcal vaccine will be given at two months, fourmonths and thirteen months of age. There will also be a catch-up cam-paign for children up to two years who have already started their immuni-sations. The vaccination schedule in the UK covers the following diseases:Diphtheria, Tetanus, Whooping cough (pertussis), Polio, Hib: vaccinationagainst the bacteria Haemophilus influenzae type B, which can causemeningitis, pneumonia, blood poisoning and infection of the epiglottis(back of the throat), Measles, Mumps, Rubella (German measles), Menin-gitis C, Pneumococcal: vaccination against the bacteria Streptococcuspneumoniae (known as pneumococcus), which can cause meningitis,pneumonia, severe ear infections (otitis media) and blood poisoning.

The vaccinations at the ages of two months and pre-school (three tofive years) are usually combined with a routine medical examination.

Two candidates enter testing in therace to find a vaccine for Hepatitis CThere is, as yet, no vaccine for Hepatitis C but two companies are developing drugs which in the futuremight provide one

Hepatitis C is a deeply unpleasant dis-ease responsible for 470,000 deathseach year around the world accordingto the World Health Organisation yetaround two thirds of people who areinfected develop no symptoms andone third clear the virus from theirbodies spontaneously.

The rest end up with a chronic formof the illness. Even then many do notknow they have got it and it is oftendiscovered accidentally. The symp-toms however can be debilitating andinclude fatigue, weight loss, musclepain, fevers, sleep disturbance, nauseaand diarrhoea as well as headaches,depression and mood swings.

If it is not treated then a third ofpatients progress to cirrhosis of theliver in less than 20 years (scarring ofthe liver that can ultimately stop itfunctioning) or liver cancer, anotherthird get cirrhosis in 30 years – therest never develop it. You contract itthrough contact with the blood of analready infected person and if out-come is a bit of a lottery, it certainly

creates massive amounts of illnessand unhappiness in those unfortunateenough to have bad cases of thesymptoms.

There are between 170 million to200 million people with some form ofthe chronic disease, according to theWHO.

The standard treatment at themoment is a combination of interfer-on and ribavirin. This works in 50 percent of cases but it is a lengthy andwearisome cure which is expensiveand often not properly completed.

Which means there is a strong needfor new alternative treatments,including combination therapies.

There is no vaccine at the momentbut two pharmaceutical companiesare working on vaccines that willtreat Hepatitis C.

The Austrian-based company Inter-cell has recently announced that ithas completed a small scale Phase IItrial of a new vaccine.

It was given in combination withthe standard treatment and the results

were encouraging with around half ofthe patients on the trial seeming tohave had a positive response. Trials ofthe drug have now been extended andinitial results of the larger trial areexpected in mid 2007.

The French drug company Trans-gene has started an earlier Phase Itrial of its Hepatitis C vaccine.

The trial will take 15 patients whohave chronic infections and givethem one injection a week.

“We believe that TG4040 is a prom-ising candidate to address the largelyunmet medical need for treatingchronic hepatitis C infection,” saidPhilippe Archinard, chief executive ofArchinard.

Transgene’s product candidate isbased on the MVA virus carryingsome of the proteins found on thehepatitis c virus. The MVA vector is ahighly attenuated strain of vaccinevirus that combines an extensive his-tory of safety with the ability to stim-ulate a strong immune response toantigens, says the company.

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Tomorrow’s vaccinespromise quick and easytreatmentsThe pace of vaccine development has accelerated dramatically over the last 20 yearsand manufacturers are researching and developing new vaccines using their knowl-edge of DNA technology and immunotherapy.

Apart from improved sanitation andthe provision of clean water, vaccina-tion has already prevented more ill-ness and death due to infectious dis-eases than any other public healthintervention. The most conspicuoussuccess story for vaccine-based medi-cine is the fight against smallpoxwhere the disease is now virtuallyeradicated because of the use of vac-cines. But some of the vaccines beingdeveloped today are for diseases thatare notoriously difficult to treat, suchas HIV/Aids, cancer, Alzheimer’s dis-ease and rheumatic disorders. Theirarrival should dramatically improveour lives.

Vaccines work by introducingmicro organisms or pathogens intothe cells of the immune system, whichthen learn to recognise and attackthem. Traditionally vaccines havecontained viruses that have been

weakened or modified to produceimmunity to a particular infectiousdisease by stimulating the production

of antibodies. When someone hasproduced sufficient antibodies tofight the disease, immunity results,

providing protection against the dis-ease for many months, for years oreven for a lifetime. Today, around 80per cent of the world’s vaccines aremanufactured in Europe. This figureincludes vaccines that are both pre-ventative as well as therapeutic. Overthe last 20 years the production meth-ods for both have undergone dramat-ic changes.

These changes include the develop-ment of combination vaccines forMeasles-Mumps-Rubella (MMR), andDipthteria-Tetanus-Pertussis (DTP), aswell as protein-conjugated bacterialpolysaccharides against Haemophilusinfluenza type b (Hib) and meningo-coccal or pneumococcal diseases.Genetic engineering has played a partby assisting in the development ofantigens - molecules that produce animmune response - for cholera vac-cines that are produced in bacteria.

The genetic engineers have alsobeen able to isolate the genetic codingfor particular proteins that protect theexterior of antigens. When insertedinto bacteria or yeast cells they pro-duce the protein in large quantities.Many micro organisms includingbacteria, viruses or parasites can beused as carriers in this genetic engi-neering process.

Today, ingestible vaccines preparedwith vegetables and fruits containingantigens are being tested againstpathogens. DNA plasmid technologyis also making great progress. This iswhere foreign genetic information isinserted into a bacterial plasmid thatis injected into the muscle or skin ofthe host. The development of a new

production method for producinginfluenza vaccines based on cell cul-tures is on the horizon. Traditionalinfluenza vaccines require chickeneggs for producing the vaccine. Cellcultures should make it possible tostart up vaccine production at anytime, independent of the availabilityof eggs. We can also look forward tothe development of a new improvedvaccine delivery system that willpainlessly introduce vaccines into theskin, without needles, such as drypowder formulations or in the case ofimmunisation against gastrointesti-nal diseases a new orally adminis-tered live-modified bacterial vaccine.

The list of other pathogens that arecurrently targeted by vaccines indevelopment is long and includes,Hepatitis B, C & E, Human papillo-mavirus (HPV) Herpes Simplex virus,Influenza, Mycobacterium tuberculo-sis, Neisseria meningitides serogroupB (the cause of meningococcal B dis-ease), the cause of malaria,Pseudomonas aeruginosa (whichseverely affects the lungs of cysticfibrosis patients), bronchitis andbronchiolitis. Although for some ofthese diseases a vaccine is alreadyavailable in each case a newer gener-ation vaccine is also currently indevelopment. In future it will not benecessary to make as many visits tothe doctor’s surgery. Combinationvaccines will reduce the number ofinjections per visit, and the totalnumber of injections overall, result-ing in reduced exposures to possibleinjection pain, less waste andincreased injection safety.

Chain of death: knowledge of virus DNA structure has aided researchers

The World Health Organisation predicts that between 4million and 5 million deaths could be prevented eachyear by 2015 through “sustained and appropriate immu-nisation efforts”. The introduction of immunisation pro-grammes is based on the common sense approach topreventing ill health. Programmes provide publichealth benefits for the individual, the population, and,through efficient use of resources, the NHS.

For us in the UK, the visible effects of infectious dis-eases such as polio and the previously immense toll of“common” childhood diseases is now rare. The numberof confirmed cases of meningitis C fell 90 per cent by2004 after the vaccine was introduced in 1997.

The UK was included on the 2004 WHO list of coun-tries likely to have eliminated indigenous poliomyelitis.And cases of congenital rubella syndrome, due to expo-sure to rubella early in pregnancy, have fallen consider-ably since the introduction of the vaccination in 1970.Recent advancements in technologies have led to thedevelopment of a new generation of vaccines targetingdiseases such as cervical cancer, shingles and rotavirusgastroenteritis.

It is an exciting time for the vaccine industry, with astrong development pipeline for vaccines that will playan important role in the future. Within the next 10 to

15 years vaccines for HIV, malaria and cancers such ascolorectal cancer and malignant melanoma are likely tobe a reality.

Vaccine research, development and manufacture is aspecialist area. There are just six companies that investin vaccine research and supply in the UK, which com-pares to over 75 pharmaceutical companies. These vac-cines companies, all members of the UK Vaccine Indus-try Group (UVIG), are an integral part of the vaccinecommunity in Europe and the rest of the world.

The majority – 90 per cent of the global production ofvaccines occurs in Europe. Furthermore, in 2004 twothirds of the global vaccine R&D, worth 1.2 billionEuros, was based in Europe. This represents over 22 percent of revenues reinvested focusing on new vaccinesand technologies.

The research, development and supply of vaccines isjust part of the picture when considering vaccinationprogrammes. Effective programmes require good coop-eration and communication among policy makers,health agencies, health care professionals, vaccinecompanies and the public. Diseases are no respecters ofgeographical boundaries and therefore local, nationaland international collaboration is vital. History sup-ports this with the confirmation in 1980 of the eradica-

tion of smallpox, and progress made towards the eradi-cation of polio.

Today communication across the world is essential inmonitoring the possible risk of an influenza pandemicand putting in place plans to manage such an event.UVIG and its members aim to work with individualsand organisations to support successful UK vaccineprogrammes. There is further opportunity to reduce theimpact of infectious disease by improving access toexisting vaccines, planning thoroughly for the intro-duction of new vaccines and targeting previouslyunmanageable infectious disease, in addition to contin-ued investment in research and development.

Good cooperation and communication among allconcerned with vaccination policies will ensure that thebenefits of vaccines in public health will be maximised.

Trade body works with others tosupport vaccine programmesFew of us have experienced first-hand the illness and death wrought by infectious diseases like polio and smallpox.This is due largely to the routine use of vaccines in public health programmes, argues the UK Vaccine Industry Group.

Founded in 2003 by liver disease specialist Pro-fessor William Rosenberg, iQur is based in the

University of Southampton with operations acrossthe UK and Europe.

Putting Patients FirstiQur offers a comprehensive sample testing servicefor diagnostic and research use for hepatitis B,hepatitis C and HIV. The company’s proprietarytest, iQur FASTTEST, delivers accurate, reliableresults to clinicians, typically within 24–48 hours,enabling them to give the best possible service totheir patients.

Director of Operations, Di Sheridan explains,“Customer service is paramount and our Diagnosticdivision pays close attention to the individual needsof our clients. Our tests are available singly or incombination, and we have introduced the use ofblood spots or saliva samples for easier collection.Results are available in a variety of formats, includ-ing via fax, e-mail or letter.”

iQur has recently launched a new non-invasivemethod of assessing liver fibrosis. Using serummarkers, the Enhanced Liver Fibrosis (ELF) Testprovides valuable information to clinicians in thediagnosis, prognosis and treatment decisions forall diseases of the liver. “This simple blood test canbe used repeatedly, with minimal patient discom-fort, to monitor disease progression and responseto therapy,” says Sheridan.

Pushing BoundariesiQur has a number of strategies for the develop-ment of new therapeutics for liver disease. Thecompany aims for a holistic approach, attemptingto treat liver damage and using the immune sys-tem to attack hepatitis viruses. Chief ScientificOfficer, William Rosenberg explains, “As the liverbecomes damaged, it lays down scar tissue and thisfibrosis limits its function and causes damage. Wehave evidence that this process can be inhibited ata molecular level, which may offer a route to effec-tive new therapies.”

Currently, no vaccine exists for hepatitis C andthose that are available for hepatitis A and B havelimited efficacy. The failure to generate a protec-tive immune response for hepatitis C is attributedto failure in education of the immune system toeliminate the hepatitis C virus.

“Using serum markers, theEnhanced Liver Fibrosis (ELF)

Test provides valuable information to clinicians in the

diagnosis, prognosis and treatment decisions for all dis-

eases of the liver”“iQur uses a system that alerts the immune systemto fragments of the virus in an “immunogenic”context,” reveals Rosenberg, “thereby training itto eradicate infection. This effectively providesthe immune system with a strong signal that

allows it to learn how to deal with the virus. Thesystem is currently in pre-clinical development,but shows significant promise.”

The company also strives to improve drug treat-ment regimens currently used for liver disease.Existing drugs used for treatment of hepatitis Chave a severe limitation caused by the side effect ofanaemia and, although increased doses of drug aremore effective at killing the virus, these amountscannot be given to patients because of the anaemiathey induce. iQur is developing a range of newchemical entities (NCE’s) which have been shownto have significant anti-viral activity without thisside effect.

Further information on business develop-ment, partnering opportunities and iQur’s

range of services can be found atwww.iqur.com or by e-mailing info@iqur.com

iQur: the liver experts – diagnostics, therapeutics, knowledgeiQur Ltd is a specialty pharmaceutical company at the forefront of international breakthroughs in the detection, treatment and monitoring of viral hepatitis and other liver diseases.

A natural progressionwww.solvayhealthcare.co.uk

• is a global healthcare business providing medicines that meetpeople’s health needs, particularly in the areas of cardiology,gastroenterology, vaccines and hormone replacement.

• invests about 15% of turnover in research and development of newmedicines.

• concentrates on developing medicines in areas of clinical needwhere Solvay feels it has an innovative contribution to make.

Solvay Pharmaceuticals has been prominent in the areaof influenza vaccines for more than 50 years now. We areone of the world’s biggest flu vaccine producers and arepresent in more than 60 countries worldwide.

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With the exception of cleandrinking water, vaccination hasproven the most effectiveintervention in reducing andpreventing sickness and deathfrom infectious diseases. Over the last half century, GlaxoSmithKlinehas developed approximately 30 vaccines toprotect against a range of diseases such asrubella and measles - diseases that can havedevastating effects on individuals, theirfamilies and society.

Within the next five years, the companyintends to introduce a further five newvaccines targeting, among others, humanpapillomavirus (HPV) - the cause of cervicalcancer - and H5N1, a strain of bird flu.

GSK has a strong history of investing in thediscovery and production of vaccines, andwill be investing hundreds of millions of

Investigating new ways to make vaccinesmore effective

pounds into research and development inthe coming years.

One outcome of this investment has beenthe development of a new generation ofsmart technology. This technology isenabling GSK to investigate vaccines in newdisease areas and different vaccineformulations to improve the way ourbodies respond to vaccination andtherefore enhance our protection.

Compounds known as adjuvants are oftenincluded in a vaccine formulation toenhance the body’s own immune response.GSK has developed a unique expertise,combining adjuvants to design systems withthe ability to elicit a strong, durable, andmore targeted immune response.

With nearly two decades of experienceworking with adjuvant systems, GSKscientists can now draw on a portfolio ofover 25 adjuvant systems in their search fornew vaccines to protect against diseases. Ofthe 20 new vaccines currently indevelopment, two-thirds include such anadjuvant system.

A number of the vaccines GSK is currentlyinvestigating are for diseases where theburden is predominantly within the

developingworld,includingtuberculosis,AIDS andmalaria – theWorld HealthOrganisation’stop threepriorities.

GSK is committed tomaking its vaccinesavailable across the globe toall who need them and it worksclosely with organisations such as theGlobal Alliance for Vaccines andImmunisations (GAVI) and Unicef thatprovide vaccines to the developing world.

In 2006, the company distributed morethan 1.1 billion doses of vaccines to 169countries. Of these, 75 per cent went to thedeveloping world at price levels that reflectthe financial capabilities of individualcountries.

GSK is committed to improving the qualityof human life by enabling people to domore, feel better, and live longer. For moreinformation visit www.gsk.com

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Why global access to vaccines isa life and death issue for many

Without a united effort by rich countries, rapid access to life-saving vaccines will remain a dream in many poorer parts of theworld and tragic levels of suffering will continue.

Cervical cancer is now the second mostcommon cancer among women and 80percent of deaths resulting from thiscancer occur in the developing worldwhere access to screening and treat-ment is extremely limited. HPV

(human papillomavirus, the virus thatcauses virtually all cases of cervicalcancer) is one of the fastest growingsexually transmitted infections world-wide with approximately 500,000 newcases reported annually.

Screening and treatment in indus-trialised countries have dramaticallyreduced cervical cancer rates over thelast 60 years, but in developing coun-tries the death rate continues to rise,not surprising as over 95 per cent ofwomen never have a pap smear. InDecember 2006 The InternationalPlanned Parenthood Federation(IPPF) Conference called for immedi-ate action to ensure a rapid globalaccess to new cervical cancer vac-cines that have the potential to save aquarter of a million lives a year. Themajor hurdles faced in deliveringthese vaccines to women in develop-ing countries are not new ones. Over95 per cent of new HIV infections forexample occur in resource limitedcountries where governments andindividuals have extremely limitedfunds to purchase vaccines and otherhealth care products. Although helpis received through UNICEF and theVaccine Fund to distribute vaccinesinternationally, additional fundingwould be needed to oversee the man-ufacture, purchase, shipping, storageand distribution of vaccines.

Poor healthcare infrastructure inmany communities where the vac-cines are needed is another huge hur-dle as there are too few health clinics,

laboratory facilities and trainedhealth care personnel in many com-munities where the vaccines areneeded. In 2000 the global Alliancefor Vaccines and Immunization –GAVI was launched to improve accessto vaccines and to accelerate thedevelopment and introduction of newvaccines in poor countries. Prior tothis in the 1980’s UNICEF had led theuniversal child immunisation initia-tive. But as the rates of immunisationincreased, attention drifted to othermatters and the rates began stagnat-ing again and even dropping. Theimpact of this saw 700,000 childrendying from measles in sub-SaharanAfrica, and rates of whooping cough,and diphtheria started to rise giving atotal of three million children dyingevery year to vaccine preventable dis-eases.

In Asia the overall impact of dis-ease is higher due to low immunisa-tion rates. GAVI has been in involvedin providing time limited funding forvaccines – encouraging poorer coun-tries to slowly take over the financingas they are able.

AIDS vaccines too, could one daybe an important tool for bringing theHIV pandemic under control – butonly if they are made available to

everyone who needs them. To be trulyeffective, an HIV/AIDS vaccine wouldhave to be readily available andaffordable for all men, women andchildren living throughout the world.

Identifying an effective vaccine isonly part of the problem. Experiencewith other vaccines has shown thatthere can be considerable delaysbetween license and actual access inthe developing world.

“There is usually a 15 – 20 yeartime delay between the time that newvaccines are approved in the west andthe time they reach developing coun-tries”, says Dr Nothemba Simelela,Director of Technical Knowledge andSupport at the IPPF. The IPPF Confer-ence in December, held at the RoyalCollege of Physicians in London wasthe first international forum toaddress the full range of issues thatimpede global access to HPV vac-cines. The meeting was convened bysix non profit organisations includingthe Rockefeller Foundation, the Inter-national Union against Cancer(PATH), and the AIDS Vaccine Advo-cacy Coalition and more than 60 keyleaders from multilateral agenciesattended including the government,and the pharmaceutical industry.

“This meeting is unique”, said Iso-bel Mortara, executive director of theInternational Union Against Cancer.“It brings the key sectors to the tablebefore the vaccines are widely in use.Partnerships across sectors and inno-vative health delivery approaches canhelp ensure global access to these newvaccines.” Perhaps its conclusionscan be used to improve access to allvaccines in the developing world.

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Vigilance thekey to keepingvaccines safeVaccine production often involves cultivating cultureson material of an animal origin but proper testing pro-cedures ensure that there is no contamination.

Before the measles vaccine waslicensed in the United States in 1963,some 400,000 cases of measles werereported on average each year. Yetbecause virtually all children contract-ed measles, it was likely that the actualnumber of cases probably approached3.5 million to 4 million cases per year, afigure equivalent to the entire numberof children born. By the early 1980s,with the arrival of the vaccination pro-gramme, the annual incidence ofreported measles cases had beenreduced by more than 99 per cent, toless than 1,500 cases and when later inthat decade, the vaccination rate

decreased and an outbreak of measlesoccurred between 1989-1991, morethan 55,000 cases and greater than 120measles-related deaths were reported inthe United States. The correlationbetween vaccination and a reduction incontagious disease is obvious. Despitethis and many other examples, vacci-nation programmes are frequentlyinterrupted by fears of the side effects ofthese vaccines. A prime example is thealleged link between MMR vaccine andautism. Having vaccine safety expertsinvestigate such cases and determinethe likelihood of causal relationshipscan help preserve the public’s faith invaccines. In the past with vaccines liketetanus and diphtheria where safetyand effectiveness were based on severalyears of data and post marketing moni-toring, to ensure that the products weresafe and potent, a variety of testingmethods were used.

As the technologies used for devel-oping vaccines have progressed, sohave the means of testing them.

Tests are now highly sensitive andable to detect potential hazards. Inaddition to these sophisticated testscurrent vaccine regulation depends ona number of other procedures to ensuresafety. According to the World HealthOrganisation these include ‘characteri-sation of starting materials by supplieraudits, cell banking, seed lot systems,compliance with the principles of goodmanufacturing practices, independentrelease of vaccines on a lot-by-lot basisby fully functional national regulatoryauthorities, demonstration of productionconsistency and enhanced pre and post-market surveillance for possible adverse

events, following the use of these vac-cines. These procedures help assure vac-cine quality, efficacy and safety.’

For those vaccines, for example, pro-duced in animal or human cell sub-strates there is great emphasis nowplaced on testing to ensure the absenceof contaminating viruses that couldcause disease in humans, such as ensur-ing that for the production of themeasles vaccine which is produced inchicken cells, the eggs themselves arefrom chickens shown to be free of theavian leukosis virus.

Increased knowledge of certain dis-eases does reveal the limitations of test-ing procedures. Currently it is knownthat some potential hazards cannot eas-ily be detected by laboratory tests. Theagents of transmissible spongiformencephalopathies (TSE’s) including thatof the bovine origin BSE which isinvolved in Creutzfeldt-Jakob disease isa good example of this. Production ofsome vaccines requires the use of rawmaterials of bovine origin which isadded to cell culture media andalthough where possible use of low risktissue is used in research where it can-not be avoided and the materials aresourced from countries that have notreported cases of BSE.

Creating a credible and effective vac-cine safety system will become evenmore important in the future. Since fewvaccine preventable diseases are eradi-cable, most immunisations will contin-ue indefinitely and obtaining accuratedata on and developing methods tominimise the risks from the vaccineswill be essential to maintaining publicacceptance of vaccinations.

Complacency – the enemy thatallows disease to sneak backSpectacularly successful immunisation programmes have been put at risk as populations turn away from vaccina-tion and memories of the horrors of the original disease fade leaving new generations exposed to infection..

Despite remarkable advances in med-ical research and treatments duringthe 20th century, infectious diseasesremain among the leading causes ofdeath worldwide. Each year vaccina-tion prevents up to three milliondeaths and 750,000 cases of perma-nent disability due to infectious dis-eases, says the Global Alliance forVaccines and Immunization, set up in2000 to improve immunisation inpoor countries.

There is a strong element of self-interest for those in the developedworld because, crudely the more vac-cinated people there are, the safer it is.Studies have shown that when the rateof vaccination drops in an area thenumbers affected by infectious dis-eases increase. So vaccination protectsnot only the individual who receives itbut also the health of the whole com-munity and when a large part of thepopulation is immunised, this can helpprevent a disease from spreading.

Whilst a few infectious diseases canbe totally eliminated through massvaccination programmes, many canbe brought under control. This wasthe case in the 1980’s during theUNICEF universal child immunisationinitiative in sub-Saharan Africa when

measles, whooping cough and diph-theria were all brought under control.But then the immunisation rate start-ed to fall and once again these dis-eases became rampant and 700,000children were dying each year fromvaccine preventable diseases. The

bacteria or viruses that cause thosediseases continue to exist, and remaina threat to the health of those who arenot protected through vaccination.

It only takes a few people who donot protect their families throughvaccination to put their own families

and non-immunised neighbours atrisk, says the Global Alliance for Vac-cines and Immunization. In higherpopulated areas, the overall impactfrom low immunisation rates is obvi-ously much greater. Urban popula-tions are growing, thereby increasingopportunities for person-to-persontransmission while public healthservices may not be equipped to dealwith some infectious outbreaks.

Today many in Europe can notreally remember measles or polio epi-demics but there is the danger ofcomplacency. As these diseases havedisappeared from our communities, itis very easy to underestimate thegrave risks of vaccine preventablediseases and begin to question thebenefits of vaccination. Especiallywhen these doubts are fuelled byrumours of the possible side effects ofvaccines.

History has demonstrated repeated-ly that when high immunisation ratesare not maintained infectious diseasesreturn and non-immunised people aremore likely to contract the disease.Whooping cough (pertussis) is a dis-ease that has largely been under con-trol, but which has reappeared eachtime that the vaccine coverage drops.

Up to 1976 there had been a dra-matic reduction in the numbers ofreported whooping cough cases inthe United Kingdom as a result of thewidespread administration of its vac-cine. Concerns about the allegedserious side effects of this vaccine ledto a dramatic fall in coverage from81 per cent to 30 per cent. This wasreflected across Europe, and in Swe-den and Italy the vaccine was virtu-ally abandoned altogether.

There was a huge increase in thenumber of reported whooping coughcases (an estimated report puts thefigure at 300,000 in the UK) and evendeath in those unvaccinated (70, inthe UK). As for the side effects, it hasstill not been possible to scientifical-ly confirm they exist. A similar situa-tion has been seen with the MMRvaccine.

In Coburg, Germany, a town with apopulation of 44,000, and only 50per cent vaccination coverage due toparental refusal to use the MMR vac-cine, a severe measles outbreak inschools saw 700 children infectedand 30 hospitalised. One of thestrongest arguments for vaccinationis that immunisation is one of themost cost effective health interven-tions in existence.

The World Health Organisation hascalculated that the eradication ofsmallpox in 1979 led to direct sav-ings of $275 million (US) per annumworldwide. Immunisation reducesthe social and financial costs oftreating diseases. It gives poor coun-tries the chance to break out of thecycle of dependence; but it is allwasted if the diseases are allowed tocreep back in developed countries asattention turns elsewhere.

Just a pin-prick: measles cases were reduced by 99 per cent in the US before vaccination rates decreased

Lest we forget: diseases that were once bought under control can get out of hand again

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A flu pandemic could kill300,000 in Britain but withcontrol measures properlyenforced that numberwould be cut by two thirds.

Each year, winter flu kills around4,000 people in the UK and between500,000 and one million around theworld. Most die from the complica-tions such as pneumonia or bronchitisthat develop as a result of a weakenedimmune system. But even in a normalyear when new and exotic strains ofthe disease are kept at bay, the virus isa cold-hearted killer ultimatelyresponsible for thousands of deaths.There are only three different influen-za viruses, but each one is variable

and comes in many different strainsand new varieties can appear andspread quite quickly.

Seasonal flu refers to the virusesthat circulate in the human popula-tion and causes widespread illnesseach winter. Avian flu in contrast is adisease which mainly affects birdsand pandemic flu occurs infrequentlywhen a new influenza virus emergeswhich is different from those recentlycirculating in the human population.It causes disease in people becausethey have little or no immunity to it.

Experts are concerned that theavian flu virus (H5N1) currently cir-culating among birds in Africa, Asiaand Europe has demonstrated theability to cross the species barrier tocause disease and death in humans.

Up to now there have been very

limited reported instances of the flupassing from person to person. If itdoes spread between people, scientistspredict it will lead to a global pan-demic, which could cause millions ofdeaths and could devastateeconomies.

Professor Maria Zambon head ofrespiratory virus unit at the HealthProtection Agency said avian flu haddifficulty replicating in human cells,but the more people who becomeinfected, the more likely the virus wasto mutate.

Since first detected in 1997, theH5N1 bird flu virus has caused 271human cases and 165 deaths. Whencompared with H5N1 virus from1997, the H5N1 now circulating ismore lethal to experimentally-infect-ed ferrets (which respond in the same

way as humans to infection) and sur-vives for longer.

Scientists have learned that thevirus can remain viable in bird drop-pings for long periods, spreadingamong birds and animals throughingestion or inhalation. For the mostpart humans have contracted it fol-lowing very close contact with sickbirds. Four different antiviral drugs-amantadine, rimantadine, oseltamivirand zanamivir are commonly used forthe treatment and prevention ofinfluenza.

However, there is evidence that theH5N1 viruses isolated from poultryand humans in Asia are resistant totwo of these. The British Governmenthas been accused of failing to listen toexpert advice by stockpiling a singledrug that might not work, to treat thepopulation.

The Royal Society and the Acade-my of Medical Sciences believe thatthe Government should be buyingsimilar quantities of a second drug,Relenza as well.

Tamiflu (oseltamir) has been chosenbecause it can be taken in tablet formbut scientists have realised that evenif it does work against H5N1, it mayneed to be given in larger doses thanoriginally intended and there will beno time to manufacture more shoulda pandemic occur, so the stock piles ofboth drugs need to be larger than atpresent.

Vaccination is high on the agendaof those experts working to preventsuch a pandemic and there has been abig change in the Government’s list ofthose needing protection.

They recommend that anyone over65 should be vaccinated especiallythose living in hospitals and carehomes, and anyone over six monthsold with low immunity as a result ofdisease or treatment.

Flu vaccines do not guarantee thatflu will not follow, but they usuallyresult in a much milder form of theinfection. Flu vaccines give immunityfor about a year to three strains of fluvirus and current vaccines work bygiving immunity to two proteinscalled haemagglutinin and neu-raminidase that are found on the sur-face of flu viruses.

However, the proteins themselveskeep mutating in a bid to fool theimmune system, making it impossiblefor vaccine manufacturers to keep upwith the creation of each new strain.

In Britain scientists are on the vergeof producing a flu vaccine that works

against all major types of the disease.It would protect against all strains ofinfluenza A, the virus behind bothbird flu and the nastiest outbreaks ofwinter flu.

It is predicted that a few injectionscould give long-lasting immunity,unlike the current vaccine, which hasto be given every year.

Scientists at Acambis’ laboratory inCambridge, together with Belgianresearchers at Flanders Interuniversi-ty Institute for Biotechnology, arefocusing their efforts on a protein,called M2, which does not mutate.The protein is found in all types ofInfluenza A, including the currentbird flu and the virus that caused the1918 Spanish flu pandemic that killedup to 50 million across the globe.

The vaccine will be tested onhumans for the first time in the nextfew months. Importantly, the vac-cines would also be quicker and easierto make than the traditional jabs,meaning vast quantities could bestockpiled against a global outbreakof bird flu. Computer modelling hassuggested that a human pandemiccould be stopped with concertedaction and enough antiviral drugs forthree million people.

Death rate slashed Measures to curb the spread of a pan-demic include flu vaccination antivi-ral drugs, restricting social contact byclosing schools, hygienic precautionssuch as wearing protective masks,washing hands and not shakinghands, and travel restrictions in andout of the country.

Professor Sir Roy Anderson, chair-man of infectious disease epidemiolo-gy at Imperial College, Londonshowed estimates that if all these con-trol measures were put in place therewould be fewer than 100,000 deathsin the UK in the event of a pandemic.If none of these precautions weretaken nearly 300,000 people coulddie. A similar pattern is predicted inthe US, with around 600,000 expectedto die without any controls in place,but only half that number if they allwere.

According to Prof. Anderson, thefatality rate of the virus in infectedhumans was one of the highest everseen; there have been 166 deathsfrom 272 cases – a 61 per cent casefatality rate. He said: “It’s a veryunpleasant virus when it gets intohumans.”

Influenza: the virus that constantly mutates to fool our immune systems

Spanish InfluenzaAn estimated one third of the world’s population was infected and had clinically apparent ill-nesses during the 1918–1919 influenza pandemic. The disease was exceptionally severe. Totaldeaths were estimated at 50 million and were arguably as high as 100 million The impact of thispandemic was not limited to 1918–1919. All influenza A pandemics since that time, and almostall cases of influenza A worldwide (excepting human infections from avian viruses such asH5N1 and H7N7), have been caused by descendants of the 1918 virus, including “drifted” H1N1viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the1918 virus, updated by subsequently incorporated avian influenza genes that code for novel sur-face proteins, making the 1918 virus indeed the “mother” of all pandemics.

Autism link with MMRA newly published Canadian study reconfirms older findings ruling out an association betweenMMR and autism. What the study found is that autism cases increased each year from 1979 to1992, but then levelled off at that point. Also, they found that the diagnosis was being made atan earlier age. The National Autistic Society has welcomed the research and concur with DrAnnabel Bently, assistant medical director BUPA Group, who said that “the rise in autism casesisn’t a ‘real’ rise, but is due to greater awareness of the condition, greater acceptance of the diag-nosis and improved record keeping.”

Although there are only three influenza viruses, each one is variable and new strains can appear and spread very quickly

AN INDEPENDENT SUPPLEMENT FROM MEDIAPLANET ABOUT VACCINES, DISTRIBUTED IN THE TIMES10

The R&D powerhousesthat pump new energyinto the vaccine marketThere are six key players among the pharmaceutical companies engaged in theresearch and development of ground-breaking new vaccines for the international mar-ket. Their work has dramatic implications for the quality of life for millions of people.

ery and Renal and Transfusion Medi-cine. Baxter acquired North AmericanVaccines in 2000 to further developits vaccine programme. Its vaccinescurrently under development includemeningococcal and streptococcal dis-ease, influenza and Lyme disease.

Their advanced vaccine technologynot only provides important newdirections for vaccines for both pae-diatric and adult use, but also has thepotential to improve the safety andefficacy of those currently available.

They have invested $170 million ina new start-of-the-art cell cultureproduction facility which will enableBaxter to produce multiple vaccinesusing the company’s proprietary pro-duction process. Baxter will then beable to produce recombinant and cellculture vaccines in one facility.

Novartis Vaccines & DiagnosticsIn March 1996, Sandoz and Ciba-Geigy, the two Swiss-based chemi-cal/life science giants joined forces.They became Novartis and at the timewas the largest corporate merger inhistory.

Novartis Vaccines & Diagnostics isa new division and is focused on thedevelopment of preventive treatmentsand tools. The division has two busi-ness units: Novartis Vaccines, andChiron, the blood testing and molecu-lar diagnostics unit.

Novartis Vaccines is the world’sfifth-largest vaccines business andthe world’s second-largest manufac-turer of flu vaccines and has impor-tant meningococcal, pediatric andtravel vaccine franchises.

The company’s portfolio of prod-

ucts includes vaccines for influenza,meningitis, rabies, tick-borneencephalitis, Haemophilus influenzaeB (Hib), polio, mumps, measles andrubella and diphtheria, tetanus andpertussis (whooping cough).

GlaxoSmithKlineOne of the world’s leading research-based pharmaceutical and healthcarecompanies. Headquartered in the UKand with operations based in the US,they are one of the industry leaders,with an estimated seven per cent ofthe world’s pharmaceutical market.

Their philosophy is that they ‘arecommitted to improving the qualityof human life by enabling people todo more, feel better and live longer.’

They market over 25 vaccinesworldwide to prevent potentially life-threatening or crippling illnesses suchas hepatitis A, hepatitis B, diphtheria,tetanus, whooping cough, measles,mumps, rubella, polio, typhoid,influenza and bacterial meningitis.

The majority of their vaccineresearch and development activitiesare conducted at GlaxoSmithKlineBiologicals in Rixensart, Belgiumwhere over 1,300 research scientistsare devoted to developing new vac-cines and more cost-effective andconvenient combination vaccines toprevent infections that cause seriousmedical problems worldwide.

They are also looking at therapeuticvaccines that may prevent relapse incancer patients.

Sanofi Pasteur MSDThe only European company dedicat-ed exclusively to vaccines and was

Baxter HealthcareThe company began operating morethan 70 years ago. Since then it has

grown into a major global healthcarecorporation with separate divisions tocover BioScience, Medication Deliv-

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founded in 1994, as a joint venturebetween Sanofi Pasteur and Merckand Co Inc.

Sanofi Pasteur MSD develops vac-cines, originating from research byboth shareholders, and ensures theyare available to people across Europe,providing protection from disease forall age groups.

They believe the main way ofachieving this goal is to develop andmake available innovative vaccinesagainst a wide spectrum of diseases.The development of safe and effectivevaccines is a long and arduousprocess from the first recognition ofan infection requiring protection tothe laboratory development of thevaccine and testing to ensure safetyin clinical trials which are carried outin three phases.

Vaccines in development includethose against human papilloma virus(HPV), the most common cause ofcervical cancer, rotavirus (the mostcommon cause of childhood diar-rhoea) and herpes zoster.

Solvay HealthcareIn 1861, Ernest Solvay, a man with apassionate interest in science,research and innovation, developed arevolutionary ammonia-soda processfor producing sodium carbonate.

The Solvay group was founded in1863 and has grown to become aglobal group of pharmaceutical andchemical companies specialising inthree sectors: Pharmaceuticals,Chemicals and Plastics.

Solvay Healthcare is based inSouthampton and has been promi-nent in the area of influenza vaccines

for more than 50 years. They are oneof the world’s biggest influenza vac-cine producers. Influvac® is used inmore than 45 countries worldwide.

Wyeth VaccinesFounded in 1926 under the nameAmerican Home Products Corpora-tion. Whilst their headquarters are inMadison, New Jersey they operate inmore than 100 countries and employ50,000 people world wide.

In 2006, Wyeth spent approximate-ly $3.1 billion on research and devel-opment, with an emphasis on phar-maceutical, vaccine and biopharma-ceutical approaches to treating andpreventing disease.

Vaccines traditionally have beentargeted to preventing disease or“treating the healthy”. Research andDevelopment at Wyeth while canteredon prevention, also seek to determinewhether certain vaccines might haveutility in treating disease.

Wyeth’s vaccine range includesconjugate vaccines against meningo-coccal group C, Haemophilus influen-zae Type b and Streptococcus pneu-moniae together with polysaccharidepneumococcal and influenza vac-cines. Wyeth Vaccines R&D also tar-gets viruses such as the humanimmunodeficiency virus (HIV) andpapilloma virus.

Important research is being carriedout in the search for immunothera-pies for Alzheimer’s disease. Teamedwith scientists from Wyeth’s smallmolecule and biopharmaceuticalsprograms, Wyeth hopes to be able tobring forward successful treatmentsto combat Alzheimer’s disease.

Revolutionising protection against two major diseases In a Cambridge-based biotechnology company, two well-kept secrets are being devel-oped that could transform the fight against infectious diseases that are both high ontoday’s medical agenda: influenza – including the pandemic threat – and the increas-ingly high-profile superbug, Clostridium difficile (C. difficile).

Acambis aims to find innovativeapproaches to significant medicalproblems, including developing thefirst-ever vaccine against C. difficileand a ground-breaking flu vaccinethat would protect against both pan-demic and seasonal influenza viruses.

A hospital-acquired bacterial infec-tion, C. difficile-associated disease(CDAD) became well known in the UKfollowing major hospital outbreaks in2004.

According to the Office of NationalStatistics, CDAD continues to be aserious and growing problem, with a69 per cent increase between 2004and 2005.

CDAD typically causes diarrhoea,but a highly virulent strain of C. diffi-cile has been found responsible forthe severe disease and higher levels ofmortality.

Dr Michel Warny, project leader forAcambis’ C. difficile vaccine pro-gramme commented, “C. difficile hasbeen a problem in hospitals fordecades. This virulent strain empha-sises the limits of current preventativemeasures such as hygiene control andtreatment with antibiotics.”

“We believe prevention is the bestdefence and are developing a vaccineto revolutionise the way C. difficile iscontrolled.”

To date, Acambis is the only com-pany to have undertaken human clin-ical trials with a C. difficile vaccine.Its programme targets both the treat-ment of current infections and,potentially, prevention of CDADitself.

Acambis’ thirst for innovation hasalso led the company to launch itself

into the single largest vaccine market:influenza. In 2005, the companyentered the flu vaccine arena with thegoal of developing a universal fluvaccine, a huge leap forward for avaccine that hasn’t changed much in60 years.

Dr Ashley Birkett, project leader ofAcambis’ influenza vaccine pro-gramme, commented: “We are work-ing toward the ‘holy grail’ of flu vac-cines. The universal flu vaccine wouldprotect against both pandemic andseasonal flu – something no vaccinehas come close to doing before.”

Acambis’ universal flu vaccine tar-gets a portion of the “A” strains of theflu virus that has remained the sameas far back as the 1918 Spanish fluand the company believes this con-served portion of the virus is thesecret to creating the most compre-hensive flu vaccine possible.

With a universal flu vaccine, therewould be no need to wait for a fluvirus strain to be identified before avaccine could be available, as is thecase today. Instead, the universal fluvaccine could be manufactured – andadministered – at any time of year.

“Moreover, a universal flu vaccinecould protect against all pandemicstrains – even those we haven’t yetseen,” Dr Birkett added. “This meansthat doses could be stockpiled inadvance, which would offer hugeadvantages to countries’ pandemic flupreparedness efforts.”

Acambis plans to start human clini-cal testing for its pandemic flu vac-cine in the next few months, the firststep toward the creation of a univer-sal flu vaccine.

The Global Fund to fight diseaseOne of the biggest challenges in fighting disease in resource- limited coun-tries is finance.Over 95 per cent of new HIV infections occur in those countries where gov-ernments have extremely limited funds to purchase vaccines and otherhealth care products. This is where the richer countries and internationalorganisations need to step in and work together to help. The Global Fund toFight Aids, Malaria and TB is one example of an international effort toexpand purchasing capacity for necessary health products. Up to now, leg-islative proposals have sought to create the necessary funds to buy vac-cines. New proposals were put forward and endorsed by the G-7 financeministers in 2005, where donor countries and organisations pre-commit tobuying AIDS vaccines for global use when these products become availableunder Advanced Market Commitments.

Missing vaccinesChildren may have missed one of their regularly requiredvaccines over the past few years, as many vaccines havebeen unavailable or in very short supply. These include vac-cines for MMR, DTaP, Hib, Varivax (chickenpox), HepatitisB, Prevnar and Td (Tetanus) and has resulted from a reduc-tion in the number of companies making vaccines and also‘production issues’, according to the US-based Centre of Dis-ease Control (CDC), where there have been ‘decreased yieldsof the biologic materials used in certain vaccines, the elimi-nation of some vaccines containing thimerosal as a preser-vative and insufficient vaccine stockpiles.’

ChickenpoxAlthough mostly a mild disorder in childhood, vari-cella tends to be more severe in adults. It is an acutehightly contagious viral disease with worldwide dis-tribution and can be fatal in newborns and in thosewith compromised immunity. Following infection thevirus remains dormant in the system and can be reac-tivated in the form of shingles. Control of varicellacan be achieved only by widespread vaccination. Mostdeveloping countries have other vaccine-preventablediseases that cause significantly greater morbidity andmortality, and varicella vaccine is not a high priorityfor routine introduction into their national immunisa-tion programmes.

Vaccine TimetableChildren in the US, currently receive 22-23 shotsbefore they enter school, including: 3 doses of Hepati-tis B, 5 doses of DTaP, 3-4 doses of Hib, 4 doses of IPV(polio), 4 doses of Prevnar, 2 doses of MMR and 1 doseof Varivax (chickenpox). In addition they may also geta yearly flu shot and the hepatitis A series of shots.

A man with a mission: Acambis is on the verge of developing a universal flu vaccine

Sanofi Pasteur MSD's commitment:

Developing innovative vaccines

Protecting all age groups with an effective,high quality range of vaccines

Conveying the unique characteristics of vaccinesand their value for health:

• Increasing doctors' and healthcare professionals'knowledge of vaccinology

• By informing and educating those involved in Public Health, and thus everyone affected by and interested in vaccination.

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