Effects of Alum Adjuvant or a Booster Dose on Immunogenicity during Clinical Trials of Group B Streptococcal Type III Conjugate Vaccines

Abstract

Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the CPS-specific immunoglobulin G (IgG) response could be boosted by administration of a second dose. Adsorption of GBS type III CPS-tetanus toxoid (III-TT) conjugate vaccine to alum did not improve the immune response to a 12.5-g dose in healthy adult recipients. Four weeks after vaccination, the geometric mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or without alum were 3.3 and 3.6 g/ml, respectively. In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-g dose 21 months later. At 4 weeks after the second dose, the GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after the primary vaccination, suggesting a lack of a booster response. However, 8 (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05 g/ml) before the first dose of III-TT conjugate exhibited a booster response to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than after the initial immunization. These results suggest that prior natural exposure to type III GBS or a related antigen may be responsible for the brisk IgG response to CPS noted in most adults after vaccination. However, a second dose of GBS III-TT conjugate vaccine may be required for adults whose initial CPS-specific IgG concentrations are very low and would also restore the initial peak-specific III CPS-IgG in responders to previous vaccination.

Clonal Analysis of Colonizing Group B Streptococcus , Serotype IV, an Emerging Pathogen in the United States

“…However, MLST was a more objective method that allowed us to compare our results with those of other laboratories and to see allelic relationships among sequence types. GBS conjugate vaccines that are being developed to prevent invasive disease may protect only against serotypes Ia, Ib, II, III, and V. Although a pentavalent vaccine that includes the more common serotypes is expected to provide protection for a high percentage of GBS cases (3,20,38), the global presence of type IV and the possibility of shifts in serotype predominance due to serotype replacement, capsular switch, or changes in bacterial virulence factors (1,9,31,40,49) necessitate ongoing surveillance of types IV and VI to VIII and the newly proposed type IX (46). Because of the emergence of invasive disease due to type IV in Minnesota, Boston, and other regions of the United States (16,27,39,45), monitoring of type IV colonization and disease in the population is warranted.…”

Recombinant Group B Streptococcus Beta C Protein and a Variant with the Deletion of Its Immunoglobulin A-Binding Site Are Protective Mouse Maternal Vaccines and Effective Carriers in Conjugate Vaccines

“…Phase 1 and phase 2 human trials have evaluated TT-containing conjugate vaccines with five serotypes of GBS that account for an estimated 98% of GBS-caused invasive disease cases in the United States (14,26,27). However, because of the concerns regarding TT overuse (10), proteins including the diphtheria mutant protein cross-reactive material (CRM 197 ) (4), a newly mutated form of diphtheria toxin (25), and the recombinant duck hepatitis B core antigen (25) have been tested as effective conjugate vaccine carriers, with all but CRM 197 tested preclinically.…”

Prevalence and Determinants of Anogenital Colonization by Group B Streptococcus Infection Among HIV Positive and Negative Women in Calabar, Nigeria

“…The war taking five years increases the child deaths under age of 5 by 13%. Also 47% of all the refugees in the world and 50% of asylum seekers and displaced people are women and girls and 44% refugees and asylum seekers are children under the age of 18 (5). As the result of wars and armed conflicts, women are…”