Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

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.

Investigating the candidacy of LPS-based glycoconjugates to prevent invasive meningococcal disease: immunology of glycoconjugates with high carbohydrate loading

“…The utility of certain maleimide (but not hydrazido) containing linkers is supported by the fact that commercial vaccines have been produced utilising similar maleimide linkers as in this study, though without the hydrazido functionality, such as the synthetic Haemophilus influenzae capsular polysaccharide serotype B vaccine, developed by Cuban scientists [12]. An immune response to the maleimide functionality could be anticipated with the Cuban vaccine if indeed the maleimide functionality was immunodominant, although this has not been reported, and the Cuban vaccine has proven to have an excellent safety profile and provokes Haemophilus influenzae serotype B specific antibody responses similar to the non-synthetic carbohydrate containing vaccine [13]. A potentially critical issue in understanding the lack of bactericidal activity of rabbit sera to wild-type meningococci, concerns the importance of the presentation of the different terminal LPS sugar structures that are characteristic of the mutants used in the candidate vaccine immunogens.…”

Investigating the potential of conserved inner core oligosaccharide regions of Moraxella catarrhalis lipopolysaccharide as vaccine antigens: accessibility and functional activity of monoclonal antibodies and glycoconjugate derived sera

“…The utility of certain maleimide (but not hydrazido) containing linkers is supported by the fact that commercial vaccines have been produced utilising similar maleimide linkers as in this study, though without the hydrazido functionality, such as the synthetic H. influenzae capsular polysaccharide serotype B vaccine, developed by Cuban scientists [35]. An immune response to the maleimide functionality could be anticipated with the Cuban vaccine if indeed the maleimide functionality was immunodominant, although this has not been reported, and the Cuban vaccine has proven to have an excellent safety profile and provokes H. influenzae serotype B specific antibody responses similar to the non-synthetic carbohydrate containing vaccine [36]. In this study although a large proportion of the immune response was apparently distracted to the maleimide/hydrazide linker, we still obtained functional antibodies as serum bactericidal assays revealed that post-immune sera were capable of killing wild-type M. catarrhalis cells at dilutions approaching 1:50 when compared to the appropriate controls and pre-immune sera.…”

Salmonella flagellin is a potent carrier–adjuvant for peptide conjugate to induce peptide-specific antibody response in mice

“…Chemical conjugation is widely used to make peptides and polysaccharides immunogenic [32][33][34][35], and also used to enhance immunogenicities of some protein antigens [27,36,37]. Although frequently used carrier proteins such as bacterial detoxified exotoxins or nontoxic exotoxin mutants as well as some bacterial outer membrane protein complexes have shown to be effective and safe in humans, their preparation is often difficult or access to them is often limited.…”