scholarly journals Safety and Immunogenicity of Capsular Polysaccharide–Tetanus Toxoid Conjugate Vaccines for Group B Streptococcal Types Ia and Ib

1999 ◽  
Vol 179 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Carol J. Baker ◽  
Lawrence C. Paoletti ◽  
Michael R. Wessels ◽  
Hilde‐Kari Guttormsen ◽  
Marcia A. Rench ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Conjugate Vaccines ◽  
Group B

scholarly journals Structural Properties of Group B Streptococcal Type III Polysaccharide Conjugate Vaccines That Influence Immunogenicity and Efficacy

1998 ◽  
Vol 66 (5) ◽  
pp. 2186-2192 ◽  
Author(s):  
Michael R. Wessels ◽  
Lawrence C. Paoletti ◽  
Hilde-Kari Guttormsen ◽  
Francis Michon ◽  
Anello J. D’Ambra ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Protective Efficacy ◽  
Molecular Size ◽  
Cross Linking ◽  
Opsonic Activity ◽  
Conjugate Vaccines ◽  
Type Iii ◽  
Protein Conjugate ◽  
Group B ◽  
Protein Cross Linking

ABSTRACT In this study, we tested the hypothesis that the immunogenicity and protective efficacy of polysaccharide-protein conjugate vaccines are influenced by three variables: (i) molecular size of the conjugate, (ii) molecular size of the polysaccharide used for conjugation, and (iii) extent of polysaccharide-to-protein cross-linking. Type III group B Streptococcus capsular polysaccharide was linked by reductive amination at multiple sites to tetanus toxoid to create a polysaccharide-protein conjugate (III-TT). A single lot of III-TT was fractionated into small, medium, and large M rpools. Whereas all three conferred protection in a maternal immunization-neonatal challenge model in mice, the smallestM r conjugate evoked less polysaccharide-specific immunoglobulin G (IgG) than the two largerM r conjugates. To test whether the molecular size of the polysaccharide used for conjugation also affected the immunogenicity of the conjugate, vaccines were synthesized using capsular polysaccharides with M rs of 38,000, 105,000, and 349,000. Polysaccharide-specific IgG responses in mice increased with the M r of the polysaccharides, and protective efficacy was lower for the smallest polysaccharide conjugate compared to the other two vaccines. Immunogenicity testing of a series of vaccines prepared with different degrees of polysaccharide-to-protein cross-linking demonstrated higher polysaccharide-specific antibody responses as the extent of cross-linking increased. However, opsonic activity was greatest in mouse antiserum raised to a moderately cross-linked conjugate, suggesting that some antibodies evoked by highly cross-linked conjugates were directed to a nonprotective epitope. We conclude that conjugate size, polysaccharide size, and degree of polysaccharide-protein cross-linking influence the immunogenicity and protective efficacy of III-TT conjugate vaccines.

scholarly journals Herd Protection against Meningococcal Disease through Vaccination

2020 ◽  
Vol 8 (11) ◽  
pp. 1675
Author(s):  
Stephen A. Clark ◽  
Ray Borrow
Keyword(s):  
Capsular Polysaccharide ◽  
High Weight ◽  
Age Groups ◽  
Invasive Disease ◽  
Current Data ◽  
Conjugate Vaccines ◽  
Herd Protection ◽  
Cast Doubt ◽  
Group B ◽  
Indirect Protection

Reduction in the transmission of Neisseria meningitidis within a population results in fewer invasive disease cases. Vaccination with meningococcal vaccines composed of high weight capsular polysaccharide without carrier proteins has minimal effect against carriage or the acquisition of carriage. Conjugate vaccines, however, elicit an enhanced immune response which serves to reduce carriage acquisition and hinder onwards transmission. Since the 1990s, several meningococcal conjugate vaccines have been developed and, when used in age groups associated with higher carriage, they have been shown to provide indirect protection to unvaccinated cohorts. This herd protective effect is important in enhancing the efficiency and impact of vaccination. Studies are ongoing to assess the effect of protein-based group B vaccines on carriage; however, current data cast doubt on their ability to reduce transmission.

scholarly journals Alpha C Protein as a Carrier for Type III Capsular Polysaccharide and as a Protective Protein in Group B Streptococcal Vaccines

1999 ◽  
Vol 67 (5) ◽  
pp. 2491-2496 ◽  
Author(s):  
Claudia Gravekamp ◽  
Dennis L. Kasper ◽  
Lawrence C. Paoletti ◽  
Lawrence C. Madoff
Keyword(s):  
Conjugate Vaccine ◽  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Surface Protein ◽  
Negative Control ◽  
Group B Streptococci ◽  
C Protein ◽  
Type Iii ◽  
Group B

ABSTRACT The alpha C protein, a protective surface protein of group B streptococci (GBS), is present in most non-type III GBS strains. Conjugate vaccines composed of the alpha C protein and type III capsular polysaccharide (CPS) might be protective against most GBS infections. In this study, the type III CPS was covalently coupled to full-length, nine-repeat alpha C protein (resulting in III-α9r conjugate vaccine) or to two-repeat alpha C protein (resulting in III-α2r conjugate vaccine) by reductive amination. Initial experiments with the III-α9r vaccine showed that it was poorly immunogenic in mice with respect to both vaccine antigens and was suboptimally efficacious in providing protection in mice against challenge with GBS. Therefore, modified vaccination protocols were used with the III-α2r vaccine. Female mice were immunized three times with 0.5, 5, or 20 μg of the III-α2r vaccine with an aluminum hydroxide adjuvant and bred. Ninety-five percent of neonatal mice born to dams immunized with the III-α2r vaccine survived challenge with GBS expressing type III CPS, and 60% survived challenge with GBS expressing wild-type (nine-repeat) alpha C protein; 18 and 17%, respectively, of mice in the negative control groups survived (P, <0.0001). These protection levels did not differ significantly from those obtained with the type III CPS-tetanus toxoid conjugate vaccine and the unconjugated two-repeat alpha C protein, which protected 98 and 58% of neonates from infection with GBS expressing type III CPS or the alpha C protein, respectively. Thus, the two-repeat alpha C protein in the vaccine was immunogenic and simultaneously enhanced the immunogenicity of type III CPS. III-α vaccines may be alternatives to GBS polysaccharide-tetanus toxoid vaccines, eliciting additional antibodies protective against GBS infection.

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

2001 ◽  
Vol 69 (11) ◽  
pp. 6696-6701 ◽  
Author(s):  
L. C. Paoletti ◽  
M. A. Rench ◽  
D. L. Kasper ◽  
D. Molrine ◽  
D. Ambrosino ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Phase 1 ◽  
Geometric Mean ◽  
Healthy Adults ◽  
Conjugate Vaccines ◽  
Type Iii ◽  
Specific Igg ◽  
Group B

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-μg 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 μg/ml, respectively. In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-μg 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 μg/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.

scholarly journals A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III

2018 ◽  
Vol 68 (12) ◽  
pp. 2079-2086 ◽  
Author(s):  
Sharon L Hillier ◽  
Patricia Ferrieri ◽  
Morven S Edwards ◽  
Marian Ewell ◽  
Daron Ferris ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Group B Streptococcus ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type Iii ◽  
Maternal Immunization ◽  
Young Infants ◽  
Group B

Abstract Background Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods Healthy, nonpregnant women aged 18–40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%–58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration NCT00128219.

scholarly journals SAFETY AND IMMUNOGENICITY OF GROUP B STREPTOCOCCAL (GBS) POLYSACCHARIDE (PS) TYPES Ia AND Ib-TETANUS TOXOID (Ia-TT; Ib-TT) CONJUGATE VACCINES IN WOMEN.▴ 980

1996 ◽  
Vol 39 ◽  
pp. 166-166 ◽  
Author(s):  
Carol J Baker ◽  
Marcia A Rench ◽  
Melissa E Hickman ◽  
Lawrence C Paoletti ◽  
Dennis L Kasper
Keyword(s):  
Tetanus Toxoid ◽  
Conjugate Vaccines ◽  
Group B

scholarly journals Group B Streptococcus Capsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccines Prepared by Different Methods for Intranasal Immunization

2001 ◽  
Vol 69 (1) ◽  
pp. 297-306 ◽  
Author(s):  
Xuzhuang Shen ◽  
Teresa Lagergård ◽  
Yonghong Yang ◽  
Marianne Lindblad ◽  
Margareta Fredriksson ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Capsular Polysaccharide ◽  
Cholera Toxin B Subunit ◽  
Small Molecular Weight ◽  
Toxin B ◽  
Conjugate Vaccines ◽  
Intranasal Immunization ◽  
Cholera Toxin B ◽  
B Subunit ◽  
Group B

ABSTRACT Group B Streptococcus (GBS) type III capsular polysaccharide (CPS III) was conjugated to recombinant cholera toxin B subunit (rCTB) using three different methods which employed (i) cystamine and N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), (ii) carbodiimide with adipic acid dihydrazide (ADH) as a spacer, or (iii) reductive amination (RA). The CPS III-rCTB conjugates were divided into large- and small-molecular-weight (M r) fractions, and the immunogenicities of the different preparations after intranasal (i.n.) immunization were studied in mice. Both large- and small-M rconjugates of CPS III-rCTBRA or CPS III-rCTBADHinduced high, almost comparable levels of CPS-specific immunoglobulin G (IgG) in serum, lungs, and vagina that were generally superior to those obtained with CPS III-rCTBSPDP conjugates or a CPS III and rCTB mixture. However, the smaller-M rconjugates of CPS III-rCTBRA or CPS III-rCTBADHin most cases elicited a lower anti-CPS IgA immune response than the large-M r conjugates, and the highest anti-CPS IgA titers in both tissues and serum were obtained with the large-M r CPS III-rCTBRA conjugate. Serum IgG anti-CPS titers induced by the CPS III-rCTBRAconjugate had high levels of specific IgG1, IgG2a, IgG2b, and IgG3 antibodies. Based on the effectiveness of RA for coupling CPS III to rCTB, RA was also tested for conjugating GBS CPS Ia with rCTB. As for the CPS III-rCTB conjugates, the immunogenicity of CPS Ia was greatly increased by conjugation to rCTB. Intranasal immunization with a combination of CPS Ia-rCTB and CPS III-rCTB conjugates was shown to induce anti-CPS Ia and III immune responses in serum and lungs that were fully comparable with the responses to immunization with the monovalent CPS Ia-rCTB or CPS III-rCTB conjugates. These results suggest that the GBS CPS III-rCTB and CPS Ia-rCTB conjugates prepared by the RA method may be used in bivalent and possibly also in multivalent mucosal GBS conjugate vaccines.

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