Nobody has made the calculation of what has been the costof this infectious disease to the economy of Siena….Perhaps there is no number that can describe the opportunities lost for many centuries……For example, we can make the hypothesis that without the plagueSiena in the meantime had grown 10 fold, to 1 million people.In this case, the cost of the missed opportunity would be > $10 billion per year, every year even today!

What was the cost of the 1348 plague to Siena?

Sometimes we have no problem in recognizing the intangible valueIn response to the bioterrorist attack, the U.S. Governmentmobilized large amounts of money, rushed to acquire the vaccinesagainst anthrax and smallpox, and signed contracts to produce moreof them even though their safety profile is inadequate by today’sstandards. Neither money nor technology were a problem. A budgetof $1.7 billion, more than the entire GAVI budget, has beensuggested for “bioterrorism” research.

We can avoid building moremonuments to Infectious Diseasesby fixing the economics

MenC conjugate vaccine (---) induces high level ofbactericidal antibodies in infants.

Plain polysaccharide (---) is a poor immunogen

Old (OMV, OMP) and novelantigens

•• Strain 2996 BZ232 1000 MC58 NGH38 394/98 F612 C11

• OMP 16000 2048 - - - - - - -

• OMV 65000 8000 - 2048 - - 32000 - -

• Novel 65000 512 4000 8000 32000 4000 8000 1024 16000

N. Meningitidis, commensal and pathogen

Obtained from R. Moxon

N. meningitidis

MenB capsular polysaccharide isa self antigen

Conventional vaccine development failed to provide a vaccinefor group B meningococcus

Immunogenicity testing inanimal models VACCINE DEVELOPMENT

TestConvalescent

sera

Antigenselection

5-15Years

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Clone genes

Testimmunogenicity

Purifycomponents

Identifycomponents

Vaccine

5-15years

Phylogenetic Tree

Reverse vaccinology for viruses

• Due to their small size, viral genomes have beenavailable for more than two decades

• however, the approach to vaccine development hasbeen conventional: only structural (envelop andcore) antigens have been usually considered forvaccine development

• Very recently the concept of reverse vaccinologyhas been applied also to viruses and all encodedproteins are being considered as potential antigens

• Promising results with HIV early proteins such asTat, Rev, Pol, etc show that the approahch is awinner also in this case

TIGR: Hervé Tettelin, John Heidelberg, Karen Nelson, Jonathan Eisen,

Karen Ketchum, Robert Dodson, William Nelson, Michelle Gwinn, Robert DeBoy, Jeremy Peterson, Erin Hickey,

Daniel Haft, Steven Salzberg, Owen White, Robert Fleischmann, Brian Dougherty, Tanya Mason, Anne Ciecko, Debbie Parksey, Eric Blair,

Henry Cittone, Emily Clark, Matthew Cotton, Terry Utterback, Hoda Khouri, Haiying Qin, Jessica Vamathevan, John Gill, Hamilton Smith

Claire Fraser, Craig Venter

Chiron Corporation:Vincenzo Scarlato, Vega Masignani,

Mariagrazia Pizza, Guido GrandiRino Rappuoli

Oxford University:Nigel Saunders, Alex Jeffries,

Derek Hood, John Peden, Li SunRichard Moxon

600 potential vaccine candidatesidentified

350 proteins successfully expressedin E.coli

344 proteins purified and usedto immunize mice

355 sera tested

91 novel surface-exposedproteins identified

28 novel proteinshave bactericidal

activity

MenB Vaccine: A GenomicApproach

vaccine candidates

Reverse vaccinology formeningococcus conclusions

• Using the genome-based approach, in 18 months wediscovered more vaccine candidates than the wholescientific community during the previous 40 years

• The antigens discovered in many cases are different innature from the ones identified by conventional vaccinedevelopment (non abundant antigens, non OMP,conserved…)

• It is too early to conclude whether we have a vaccine formeningococcus B, however we never had data which areso promising as the ones we have now.

• It is likely that by 2010 we will have vaccines against allforms of meningococcal meningitis, a new milestone in thehistory of medicine