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

  title={Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers},
  author={Gilda Tora{\~n}o and Mar{\'i}a Eugenia Toledo and Alberto Baly and Violeta Fern{\'a}ndez-Santana and Francisco Rodr{\'i}guez and Yunia Calvo {\'A}lvarez and Teresita Serrano and Alexis Musachio and Ibis Hern{\'a}ndez and Eugenio Hardy and Arlene Rodr{\'i}guez and H{\'e}ctor Pablo Hernandez and Arı́stides Aguilar and Raydel Mart{\'i}nez S{\'a}nchez and Manuel D{\'i}az and Verena Muzio and Jorgelina Dfana and Maria C. Rodr{\'i}guez and L{\'a}zaro E. Heynngnezz and vicente Verez-Bencomo},
  journal={Clinical and Vaccine Immunology},
  pages={1052 - 1056}
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… 
Hib Vaccines: Past, Present, and Future Perspectives
Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.
Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults
The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens, which is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigen.
Use of immuno assays during the development of a Hemophilus influenzae type b vaccine for technology transfer to emerging vaccine manufacturers
The anti-PRP IgG ELISA was developed as part of the immunogenicity test, used to demonstrate the ability of the Hib conjugate vaccine to elicit a T-cell dependent immune response in mice.
Glycoconjugate vaccines: an update
Accessibility of these glycoconjugate vaccines in resource poor regions, which bear the highest disease burden from these pathogens, remains challenging largely due to high vaccine pricing.
mmunogenicity and safety of a single intramuscular dose of a iphtheria – tetanus toxoid ( Td ) vaccine ( GC 1107 ) in Korean adults
In conclusion, GC1107 was well tolerated and provided significant boosts of anti-tetanus and anti-diphtheria antibodies and there were no significant differences between the two active treatments.
An open-label, single-arm, phase I study to evaluate the safety and immunogenicity of LBVH0101, a new Haemophilus influenzae type b tetanus toxoid conjugate vaccine, in healthy adult volunteers
LBVH0101 appeared to be safe and well-tolerated and showed good immunogenicity in Korean healthy adults and the GMT of anti-PRP antibody at post-vaccination was approximately 98 times higher than that of pre- vaccination.
Meningococcal Vaccines: Current Status and Emerging Strategies
Current meningococcal vaccines are described and some recent research discoveries that may transform vaccine development against N. meningitidis in the future are discussed.
Recent advances on smart glycoconjugate vaccines in infections and cancer.
The latest advancements in development of vaccines against glycan epitopes to gain selective immune responses are discussed, and an overview on the role of different immunogenic constructs in improving glycovaccine efficacy is provided.


A Synthetic Conjugate Polysaccharide Vaccine Against Haemophilus influenzae Type b
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) demonstrate that access to synthetic complex carbohydrate–based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.
Safety and immunogenicity of Haemophilus influenzae type B polysaccharide-diphtheria toxoid conjugate vaccine in adults.
Both vaccines were well tolerated with no fever or systemic reactions, and a single dose of PRP-D induced levels of IgG antibody to PRP three times that observed with PRP alone one month after the first inoculation.
A Synthetic Conjugate Polysaccharide Vaccine Against Haemophilusinfluenzae Type B
Synthetic PRP (sPRP) conjugated to protein was shown to be capable of binding antibody from the serum of children immunized with commercial Hib conjugate vaccine.
Antigenicity and Immunogenicity of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b
The antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals are described and these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity.
Immunogenicity of Haemophilus influenzae type b polysaccharide--diphtheria toxoid conjugate vaccine in adults.
Immunogenicity and reactogenicity of four Haemophilus influenzae type b capsular polysaccharide vaccines in Finnish 24-month-old children.
The immunogenicity of all these preparations in 24-month-old Finnish children was compared, and the now recommended dose of 25 micrograms did not give results differing from those after a 12.5-micrograms dose used in 1974.
A strategy for rational design of fully synthetic glycopeptide conjugate vaccines
The results of this study clearly demonstrate that coupling a carbohydrate hapten to a peptide can provide T- cell help and convert it into a T-cell-dependent antigen.
Antibody responses to four Haemophilus influenzae type b conjugate vaccines.
Serum antibody responses to four Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines (PRP-D, HbOC, C7p, and PRP-T) were studied and compared in 175 infants, 85 adults and
Functional Antibody Activity Elicited by Fractional Doses ofHaemophilus influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate–Tetanus Toxoid Conjugate)
Fractional doses elicit similar functional antibody activities in infants with ≥2 μg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full and one-half or one-third of the labeled concentration, respectively, which offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.
Immunogenicity in infants of a vaccine composed of Haemophilus influenzae type b capsular polysaccharide mixed with DPT or conjugated to diphtheria toxoid.
Compared with previously published data of children immunized with one dose of PRP at 18 months, the mean level of antibody to PRP in the PRP-D group at 19 months was significantly (P less than .001) higher, whereas that in thePRP + DPT group was not.