scholarly journals Evidence of Extended Thermo-Stability of Typhoid Polysaccharide Conjugate Vaccines

2021 ◽  
Vol 9 (8) ◽  
pp. 1707
Author(s):  
Fang Gao ◽  
Kay Lockyer ◽  
Alastair Logan ◽  
Sarah Davis ◽  
Barbara Bolgiano ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Structural Changes ◽  
Capsular Polysaccharide ◽  
Elevated Temperatures ◽  
Storage Temperature ◽  
Molecular Size ◽  
Cold Chain ◽  
Conjugate Vaccines ◽  
Vi Capsular Polysaccharide ◽  
Thermo Stability

Typhoid conjugate vaccines (TCV) are effective in preventing enteric fever caused by Salmonella enterica serovar Typhi in Southeast Asia and Africa. To facilitate vaccination with the Vi capsular polysaccharide–tetanus toxoid conjugate vaccine, Typbar TCV, and allow it to be transported and stored outside a cold chain just prior to administration, an extended controlled-temperature conditions (ECTC) study was performed to confirm the quality of the vaccine at 40 °C for 3 days at the end of its shelf-life (36 months at 2–8 °C). Studies performed in parallel by the vaccine manufacturer, Bharat Biotech International Limited, and an independent national control laboratory (NIBSC) monitored its stability-indicating parameters: O-acetylation of the Vi polysaccharide, integrity of the polysaccharide–protein conjugate, and its molecular size and pH. ECTC samples stored at 40 °C and 45 °C in comparison with control samples stored at 4 °C and 55 or 56 °C, were shown to have stable O-acetylation and pH; only very slight increases in the percentage of free saccharide and corresponding decreases in molecular size were observed. The deoxycholate method for precipitating conjugated polysaccharide was very sensitive to small incremental increases in percentage of free saccharide, in line with storage temperature and duration. This extended ECTC study demonstrated minimal structural changes to the Vi polysaccharide and conjugate vaccine and a stable formulation following extended exposure to elevated temperatures for the desired durations. This outcome supports the manufacturer’s ECTC claim for the vaccine to be allowed to be taken outside the cold chain before its administration.

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 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 Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines.

1994 ◽  
Vol 62 (10) ◽  
pp. 4440-4444 ◽  
Author(s):  
S C Szu ◽  
D N Taylor ◽  
A C Trofa ◽  
J D Clements ◽  
J Shiloach ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Conjugate Vaccines ◽  
Protein Conjugate ◽  
Vi Capsular Polysaccharide

Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine

Vaccine ◽  
2012 ◽  
Vol 30 (6) ◽  
pp. 1023-1028 ◽  
Author(s):  
So Jung An ◽  
Yeon Kyung Yoon ◽  
Sudeep Kothari ◽  
Deok Ryun Kim ◽  
Jeong Ah Kim ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Immune Suppression ◽  
Capsular Polysaccharide ◽  
Vi Capsular Polysaccharide

scholarly journals A Three Component Synthetic Vaccine Containing a β-Mannan T-Cell Peptide Epitope and a β-Glucan Dendritic Cell Ligand

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1961 ◽  
Author(s):  
David Bundle ◽  
Eugenia Paszkiewicz ◽  
Hassan Elsaidi ◽  
Satadru Mandal ◽  
Susmita Sarkar
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Click Chemistry ◽  
Conjugate Vaccine ◽  
Pathogenic Bacteria ◽  
Capsular Polysaccharide ◽  
Cell Epitope ◽  
Quarter Century ◽  
Peptide Epitope ◽  
Conjugate Vaccines

Glycoconjugates prepared from the capsular polysaccharide of several pathogenic bacteria and carrier proteins, such as CRM 197 or tetanus toxoid, have been one of the most successful public health measures to be implemented in the last quarter century. A crucial element in the success of conjugate vaccines has been the recruitment of T-cell help and systematic induction of a secondary immune response. The seminal discovery, that degraded polysaccharide fragments with attached peptide are presented to the T-cell receptor of carbohydrate specific T-cells by MHC-II molecules that bind to the peptide component of degraded vaccine, suggests potentially novel designs for conjugate vaccines. A fully synthetic conjugate vaccine was constructed from a 1,2-linked β-mannose trisaccharide conjugated to a T-cell peptide, previously shown to afford protection against Candida albicans. This combined B- and T-cell epitope was synthesized with a C-terminal azidolysine residue for subsequent conjugation by click chemistry. Four copies of a β-1,3 linked hexaglucan dendritic cell epitope were conjugated to an asymmetric dendrimer bearing an alkyne terminated tether. Click chemistry of these two components created a conjugate vaccine that induced antibodies to all three epitopes of the fully synthetic construct.

scholarly journals Murine Immune Responses to Neisseria meningitidis Group C Capsular Polysaccharide and a Thymus-Dependent Toxoid Conjugate Vaccine

1998 ◽  
Vol 66 (11) ◽  
pp. 5450-5456 ◽  
Author(s):  
Leonard J. Rubinstein ◽  
Pablo A. García-Ojeda ◽  
Francis Michon ◽  
Harold J. Jennings ◽  
Kathryn E. Stein
Keyword(s):  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Pathogenic Bacteria ◽  
Capsular Polysaccharide ◽  
Immunoglobulin M ◽  
Mouse Strains ◽  
Delayed Response ◽  
Conjugate Vaccines ◽  
Protein Conjugate ◽  
Infants And Young Children

ABSTRACT The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny. The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases. We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization. The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1. A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine. The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals. Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate. The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone. These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting.

scholarly journals Rotavirus spike protein ΔVP8* as a novel carrier protein for conjugate vaccine platform with demonstrated antigenic potential for use as bivalent vaccine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wook-Jin Park ◽  
Yeon-Kyung Yoon ◽  
Ji-Sun Park ◽  
Ruchirkumar Pansuriya ◽  
Yeong-Jae Seok ◽  
...  
Keyword(s):  
Immune Responses ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Spike Protein ◽  
Carrier Protein ◽  
Vaccine Platform ◽  
Bivalent Vaccine ◽  
Polysaccharide Antigens ◽  
Vi Capsular Polysaccharide ◽  
Functional Antibodies

AbstractConjugate vaccine platform is a promising strategy to overcome the poor immunogenicity of bacterial polysaccharide antigens in infants and children. A carrier protein in conjugate vaccines works not only as an immune stimulator to polysaccharide, but also as an immunogen; with the latter generally not considered as a measured outcome in real world. Here, we probed the potential of a conjugate vaccine platform to induce enhanced immunogenicity of a truncated rotavirus spike protein ΔVP8*. ΔVP8* was covalently conjugated to Vi capsular polysaccharide (Vi) of Salmonella Typhi to develop a bivalent vaccine, termed Vi-ΔVP8*. Our results demonstrated that the Vi-ΔVP8* vaccine can induce specific immune responses against both antigens in immunized mice. The conjugate vaccine elicits high antibody titers and functional antibodies against S. Typhi and Rotavirus (RV) when compared to immunization with a single antigen. Together, these results indicate that Vi-ΔVP8* is a potent and immunogenic vaccine candidate, thus strengthening the potential of conjugate vaccine platform with enhanced immune responses to carrier protein, including ΔVP8*.

scholarly journals Pediatric Invasive Pneumococcal Disease Three Years after PCV13 Introduction in the National Immunization Plan—The Continued Importance of Serotype 3

2021 ◽  
Vol 9 (7) ◽  
pp. 1428
Author(s):  
Catarina Silva-Costa ◽  
Joana Gomes-Silva ◽  
Lúcia Prados ◽  
Mário Ramirez ◽  
José Melo-Cristino ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Antimicrobial Resistance ◽  
Conjugate Vaccine ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Molecular Methods ◽  
Vaccine Uptake ◽  
Serotype Distribution ◽  
Conjugate Vaccines ◽  
National Immunization

The introduction of pneumococcal conjugate vaccines PCV7 and PCV13 led to decreases in incidence of pediatric invasive pneumococcal disease (pIPD) and changes in serotype distribution. We evaluated the consequences of higher vaccine uptake after the introduction of PCV13 in the National Immunization Plan (NIP) in 2015. Besides culture and conventional serotyping, the use of molecular methods to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 30% of all pIPD (n = 232) in 2015–2018. The most frequently detected serotypes were: 3 (n = 59, 26%), 10A (n = 17, 8%), 8 (n = 16, 7%) and 19A (n = 10, 4%). PCV13 serotypes still accounted for 46% of pIPD cases. Serotypes not included in any currently available conjugate vaccine (NVT) are becoming important causes of pIPD, with the increases in serotypes 8 and 33F being of particular concern given the importance of serotype 8 in adult IPD and the antimicrobial resistance of serotype 33F isolates. This study highlights the importance of using molecular methods in pIPD surveillance since these allowed a better case ascertainment and the identification of serotype 3 as the leading cause of pIPD. Even in a situation of vaccine uptake >95% for 3 years, PCV13 serotypes remain important causes of pIPD.

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