Towards the total synthesis of novenamine and its analogues with modifications at C-4 and C-5

Includes bibliographical references.Novenamine, a known antibacterial agent, is composed of 3-0-carbamoyl noviose (novobiose) glycosidically linked to a 4-hydroxy-3-amino-coumarin unit. Its activity as a DNA-gyrase inhibitor and the absence of analogues containing 4-epi-noviose provided the rationale for developing new synthetic routes to these analogues. This thesis describes the total synthesis of the methyl glycosides of noviose and C-4-epi-noviose, methodology for the introduction of the C-3 carbamoyl group to both isomers, an alternative synthesis of the coumarin component, progress towards a C-5 analogue of 4-epi-noviose and a model study of methodology for the glycosidic coupling of the coumarin unit to suitably activated sugars

Development of a pentavalent Group B Streptococcus (GBS) glycoconjugate vaccine in Africa

A vaccine against Group B Streptococcus (GBS), utilized in a maternal immunization strategy to reduce the burden of GBS mortality and morbidity in infants, has potential for use all over the world, but would have the greatest impact in low-resource countries that have limited access to interventions. Currently there is no vaccine against GBS. The Biovac Institute (Biovac), a private public partnership in South Africa, is developing a pentavalent, polysaccharide-protein conjugate vaccine (PCV) against GBS — using state-of-the-art technology and targeting the most common strains. A vaccine providing more than 90 % coverage against GBS infection would need to include at least 5 serotypes including serotypes Ia, Ib, II, III and V. Production of a low-cost pentavalent vaccine would require optimization of unit processes to achieve high yields without compromising product quality. The presentation will describe (1) the selection of high capsular polysaccharide (CPS) producing isolates; (2) development of manufacturing processes to produce CPS for serotypes Ia, Ib, II, III and V; (3) development of a glycoconjugate process, which involves covalently linking the CPS to a carrier protein; (4) results of a monovalent conjugate vaccine mouse study; and (5) further animal and clinical studies planned. While the GBS project affords Biovac the opportunity to establish end-to-end vaccine product development capability, equally importantly, it will also begin to shift the paradigm regarding Africa by demonstrating that vaccine projects of this complexity and magnitude can be done in Africa by Africans. It will contribute significantly to advancing Africa’s capability to respond to vaccine epidemics and infectious diseases of regional relevance

Development of a pentavalent Group B Streptococcus (GBS) glycoconjugate vaccine in Africa

A vaccine against Group B Streptococcus (GBS), utilized in a maternal immunization strategy to reduce the burden of GBS mortality and morbidity in infants, has potential for use all over the world, but would have the greatest impact in low-resource countries that have limited access to interventions. Currently there is no vaccine against GBS. The Biovac Institute (Biovac), a private public partnership in South Africa, is developing a pentavalent, polysaccharide-protein conjugate vaccine (PCV) against GBS — using state-of-the-art technology and targeting the most common strains. Please click Download on the upper right corner to see the full abstract. Please click Additional File below for the presentation

Sublingual immunisation with GBS serotype III capsular polysaccharide-tetanus toxoid conjugate vaccine induces systemic and mucosal antibody responses which are opsonophagocytic and inhibit GBS colonisation of vaginal epithelial cells

No vaccines are currently licensed against Group B streptococcus (GBS), an important cause of morbidity and mortality in babies and adults. Using a mouse model, and in vitro opsonophagocytosis and colonisation assays, we evaluated the potential of a sublingually-administered polysaccharide-conjugate vaccine against GBS serotype III. Sublingual immunisation of mice with 10 µg of GBS conjugate vaccine once a week for 5 weeks induced a substantial systemic IgG anti-polysaccharide response which was similar to the level induced by subcutaneous immunsation. In addition, sublingual immunisation also induced mucosal (IgA) antibody responses in the mouth, intestines and vagina. Immune sera and intestinal washes were functionally active at mediating killing of the homologous GBS serotype III in an opsonophagocytosis assay. In addition, intestinal and vaginal washes inhibited the colonisation of mouse vaginal epithelial cells by the vaccine homologous strain. These results suggest that, in addition to the induction of high levels of IgG antibodies that could be transduced from the immunised mother to the foetus to protect the newborn against GBS infection, sublingual immunisation can elicit a substantial mucosal antibody response which might play an important role in the prevention of GBS colonisation in immunised women, thereby eliminating the risk of GBS transmission from the mother to the baby during pregnancy or at birth

Immune responses against group B Streptococcus monovalent and pentavalent capsular polysaccharide tetanus toxoid conjugate vaccines in Balb/c mice

Summary: Immunization of pregnant women with Group B Streptococcus (GBS) capsular polysaccharide (CPS) conjugate vaccine (CV) could protect young infants against invasive GBS disease. We evaluated the immunogenicity of investigational five GBS monovalent (serotypes Ia, Ib, II, III, and V) CPS-tetanus toxoid (TT)-CV with adjuvant and GBS pentavalent CPS-TT-CV with adjuvant (GBS5-CV-adj) and without adjuvant (GBS5-CV-no-adj), in Balb/c mice. Aluminum phosphate was the adjuvant in the formulations, where included. The homotypic immunoglobulin G (IgG) geometric mean concentration (GMC) and opsonophagocytic activity (OPA) geometric mean titer (GMT) did not differ after the third dose of the GBS5-CV-adj vaccine compared with the monovalent counterparts for all five serotypes. The GBS5-CV-adj induced higher post-vaccination serotype-specific IgG GMCs and OPA GMTs compared to GBS5-CV-no_adj. The GBS5-CV with and without adjuvant should be considered for further development as a potential vaccine for pregnant women to protect their infants against invasive GBS disease