1. Center for Biomolecular Chemistry
Vicente Verez Bencomo*, Violeta Fernandez Santana, Maria del Carmen Rodriguez Montero and Yury Valdes Balbin
Vicente Verez Bencomo*, Violeta Fernandez Santana, Maria del Carmen Rodriguez Montero and Yury Valdes Balbin
Vicente Verez Bencomo*, Violeta Fernandez Santana, Maria del Carmen Rodriguez Montero and Yury Valdes Balbin
Vicente Verez Bencomo*, Violeta Fernandez Santana, Maria del Carmen Rodriguez Montero and Yury Valdes Balbin
Vicente Verez Bencomo*, Violeta Fernandez Santana, Maria del Carmen Rodriguez Montero and Yury Valdes Balbin
From synthetic oligosaccharides to human vaccines: The language of translational research
Vicente Verez Bencomo
Center for Biomolecular Chemistry
Habana, Cuba

2. 1980 ties

3. The rol of carbohydrate in recognition process
Capsular polysaccharides (CPS) of bacteria are very
important in pathogenesis
Antibodies against the CPS are protective
Advance in carbohydrate chemistry and biochemistry
Analytical methods
Modification of natural glycoconjugates
Synthesis of oligosaccharides

4. Leprosy diagnostic
Haemophilus influenzae type b glycoconjugate vaccine
Pneumococcal conjugate vaccine
Very Small Size Particles as a potent adjuvant in cancer treatment

5. Incubation time before clinical Symptoms: several years
Mycobacterium leprae
Incubation time before clinical
Symptoms: several years

6. a phenolic glycolipid recognised by antibodies from infected persons
1983 P. Brenan isolated from
Mycobacterium leprae
a phenolic glycolipid recognised by
antibodies from infected persons

7. J. Mariño-Albernas, V.Verez-Bencomo,
Carbohydr.Res.,1988, 183,

8. Institute of Tropical Medicine Pedro Kouri Center for Immunoessays
MINSAP
Antibodies in the serum of subclinical
Infected patients
CIE-UMELISA
UMELISA-HANSEN
Detection of seropositive
chemotherapy
Leprosy was reduced in Cuba and declared non-endemic
J. Mariño-Albernas, V.Verez-Bencomo, Carbohydr.Res.,1988, 183,

9. Haemophilus influenzae type b
Major children pathogen:
meningitis, pneumonia, sepsis

10. P.W.Andersson et al, J. Immunology 1989, 142, 2464-8
HibTITER Hib Wyeth Vaccines
PedvaxHIB Hib Merck
ActHIB Hib Sanofi Pasteur
ProHIBIT Hib Connaught Laboratories
P.W.Andersson et al, J. Immunology 1989, 142,
S. Pillai et al, Infection Immunity 1991, 59,
C.C.A.M.Peters et al, Infection Immunity 1992, 60,

11. Classical approach (90-ties) Van Boom, Just, Norberg, Verez-Bencomo

12. Verez Bencomo et al Carbohydrate Vaccines, ACS Symposium series 989,61-74

13. V. Fernandez-Santana et al, Glycoconjugate J. 1998, 15, 549-553

16. N type participants doses dates
Clinical Trials
N type participants doses dates
Phase I adults 1 Aug/01 Sept/01
Phase I 133 children 1 Feb/02 Mar/02
3 Phase I 40 adults 1 Mar/02 Apr/02
4 Phase I 114 infants 3 Apr/04 Sept/02
5 Phase II 1041 children 1 May/02 Jun/02
6 Phase II infants 3 Aug/02 Apr/03
7 Booster 75 infants 1 Jul/03 Aug/03
8 Booster 250 infants 1 Mar/04 May/04
IPK, CIGB, CPH Camaguey, CIGB Camaguey

18. Verez Bencomo et al, Science 2004, 521-524
Since January 2004
Number of Hib-meningitis confirmed cases
Pentavalent DPT-Hb + Hib
Licenced in 2006
WHO prequalification 2009
Verez Bencomo et al, Science 2004,

19. The main driven force was the social need
Center for Genetic Engineering and Biotechnology
Institute for Tropical Medicine “Pedro Kouri”
The main driven force was the social need
Finlay Institute
Center for Bioproduction (BioCen)
Provincial Hygiene Center of Camaguey

20. Secondary driven force
Epidemiology
Social needs
Price
market
Revenues
Social Impact
Provide more health
Secondary driven force
Market
Deep contradiction
“blockbuster”
Strategy
Increase the revenues
Main driven force

21. Las 15 vacunas mas vendidas del 2012
MM USD
Prevnar 13
3,718
Zostavax
651
Gardasil
1,900
Rotateq
648
PentAct-Hib
1,522
Synflorix
587
Infanrix
1,183
Pneumovax
580
Fluzone
1,152
Rotarix
549
Hepatitis franchise
986
Adacel
469
Varivax
846
Prevnar-7
399
Menactra
735
6,921

22. Heptavalent Conjugate vaccine
Composition
PS 1 conjugate to TT 2 mg
PS 5 conjugate to TT 2 mg
PS 6B conjugate to TT 4 mg
PS 14 conjugate to TT 2 mg
PS 18C conjugate to TT 2 mg
PS 19F conjugate to TT 2 mg
PS 23F conjugate to TT 2 mg
TT 24 mg
Aluminum phosphate 125 mg
Sodium chloride
thiomersal
One dose 0,5 mL

23. Evaluación realizada en el laboratorio de referencia de la OMS en Londres (OPS)

24. ¡La vacuna cubana protege al mismo nivel!

25. The Center for Molecular Immunology dedicated to cancer
immunotherapy have develop in the nineties a VSSP technology

26. Neisseria meningitidis Outer Membrane Protein Very Small Size Particle
GM3 ganglioside +
Neisseria meningitidis Outer Membrane Protein
complex
DETERGENT
DETERGENT
Self-organized
nanoparticle
VSSP
Very Small Size Particle
Size nM
Zeta (mV) -(45-60)
Estevez F, et al
Vaccine , 20;, 190-7

27. Several tumor-associated carbohydrate antigens are well known
Can we revisited some of them
more efficiently with VSSP technology?

28. CQB-601 GM2/VSSP CQB-602 LeY/VSSP CQB-603 GD2/VSSP Proof of concept
Synthesis of the ganglioside
VSSP preparation
Preliminary physico-chem. and biol. evaluation
Anti-Ganglioside analytical tools.
Tumor models
The new VSSP inherit the previous
immunostimulating properties
Display a new antitumor specific properties