[Show abstract][Hide abstract] ABSTRACT: Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have
been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this
important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and
infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers
under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety
and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed
for the control vaccine.
Full-text · Article · Oct 2006 · Clinical and Vaccine Immunology
[Show abstract][Hide abstract] ABSTRACT: Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the
availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens
is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being
cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several
H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity,
and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts
of the world and remains our major goal.
Full-text · Article · Jan 2005 · Infection and Immunity
[Show abstract][Hide abstract] ABSTRACT: Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.