A Canadian Success Story: Overcoming scientific and logistical problems in the development of NeisVac-C Dr. Harold J. Jennings NRC-IBS

Age specific rates for meningococcal infection UK, Public Health Laboratory Services. Compiled by D. Jones

Structures of The Capsular Polysaccharides of N. meningitidis O ‖  6)-  D -ManpNAc(1-O-P-O- 3  AcO  8)-  D -NeupNAc(2   9)-  D -NeupNAc(2  8  AcO  9)-  D -NeupNAc(2   6)-  D -Galp(1  4)-  D -NeupNAc(2   6)-  D -Glcp(1  4)-  D -NeupNAc(2  (contains OAc groups) GroupStructure A B C C(OAc - ) W-135 Y

History of the Development of NRC Conjugate Vaccines 1990NAVA Incorporated in Canada by merging BioChem/ NRC technology with AMVAX (U.S.). BioChem Pharma retained Canadian rights. 1992NAVA/ NRC vs. American Cyanamid (Praxis). U.S. Courts of Appeal infringement of U.S. Patent 4,356,170.

HPA (CDSC) E. Miller et al Laboratory Confirmed Cases of Meningococcal Disease (by quarter) England & Wales.

History of the Development of NRC Conjugate Vaccines 2000Baxter Int. acquired NAVA following marketing of Group C meningococcal vaccine. 2001Shire acquired BioChem Pharma. Retained Canadian rights on NRC technologies. 2004ID Biomedical acquired Shire’s vaccine business. Retained Canadian rights on NRC technologies

Prevalence of Group B Streptococcus disease isolates Ia 38.8% Ib 8.5% II 7.0% III 28.7% V 14.7% VII 0.8% NT 1.6%

→4)  D-Glcp-(1→4)  D-Galp-(1→ 3 ↑ 1  D-NeupNAc-(2→3)  D-Galp-(1→4)  D-GlcpNAc →4)  D-GlcpNAc-(1→3)  D-Galp-(1→4)  D-Glcp-(1→3)  D-Glcp-(1→2)  D-Galp-(1→ 6 3 ↑ ↑ 1 2  D-Galp  D-NeupNAc →4)  D-Glcp-(1→6)  D-GlcpNAc-(1→3)  D-Galp-(1→ 4 ↑ 1  D-NeupNAc-(2→3)  D-Galp →4)  D-Glcp-(1→4)  D-Galp-(1→4)  D-Glcp-(1→ 6 4 ↑ ↑ 1 1  D-NeupNAc-(2→3)  D-Galp-(1→4)  D-GlcpNAc  D-Glcp Structures of The Capsular Polysaccharides of Group B Streptococcus Ia Ib III II V →4)  D-Glcp-(1→4)  D-Galp-(1→ 3 ↑ 1  D-NeupNAc-(2→3)  D-Galp-(1→3)  D-GlcpNAc

Protection of infant mice by placentally transferred polysaccharide (PS) specific antibody Vaccine Tetanus Toxoid (TT) III PS III PS and TT III PS-TT Conjugate Mothers Vaccinated Progeny Challenged Survivors 0 27

Recent history of the development of Group B meningococcal- conjugate vaccine 1999: Aventis Pasteur sub-licensed NRC technology for the development of a chemically modified group B meningococcal polysaccharide- conjugate vaccine 2002: Aventis Pasteur carried out a limited trial of the conjugate vaccine on a few male volunteers using alum as adjuvant (poor bactericidal activity) 2003: Aventis Pasteur dropped the above sub-license because of perceived safety concerns

“Further consideration by Aventis-Pasteur experts, in- house, led to the conclusion that there could be sustained difficulties for “proving” safety to licensing authorities and the general public. Moreover, because of the plausibility of the perceived risk, the vaccine could become the focus for anti-vaccine groups with a constant threat of litigation from those who “suspect” they may have been adversely affected.” 1 1 : Decision by the Safety Consultation Committee- Aventis-Pasteur SA

Recent history of the development of Group B meningococcal- conjugate vaccine 2004: Baxter dropped the license to NRC technology on chemically modified group B meningococcal- conjugate vaccine 2004: BioVeris licensed NRC technology on chemically modified group B meningococcal- conjugate vaccine

Royalty Revenues