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 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 Exploring the role of competition induced by non-vaccine serotypes for herd protection

2017 ◽  
Author(s):  
G. L. Masala ◽  
M. Lipsitch ◽  
C. Bottomley ◽  
S. Flasche
Keyword(s):  
Disease Burden ◽  
Vaccine Coverage ◽  
Conjugate Vaccines ◽  
Effective Coverage ◽  
Vaccine Serotypes ◽  
Herd Protection ◽  
Vaccine Type ◽  
Vaccine Impact ◽  
Indirect Protection

AbstractThe competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine serotype (VT) prevalence. We aim to investigate if, consequently, the indirect protection of higher valency vaccines could fall short of the profound effects of current formulations.We compare three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in <5y old children of 40%. We simulate vaccines of increasing valency by adding serotypes in order of their competitiveness and explore their ability to reduce VT carriage by 95% within 10 years after introduction.All models predict that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage * vaccine coverage) needed to eliminate vaccine type carriage increases with increasing valency. One model predicts this effect to be modest while the other two predict that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored.Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

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 Non-invasive pneumococcal disease and antimicrobial resistance: vaccine implications

2002 ◽  
Vol 128 (1) ◽  
pp. 21-27 ◽  
Author(s):  
M. H. KYAW ◽  
S. CLARKE ◽  
I. G. JONES ◽  
H. CAMPBELL
Keyword(s):  
Antimicrobial Resistance ◽  
Clinical Isolate ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Laboratory Data ◽  
Age Groups ◽  
Invasive Disease ◽  
Polysaccharide Vaccine ◽  
Conjugate Vaccines ◽  
Non Invasive

We reviewed laboratory data on non-invasive pneumococcal isolates reported from all diagnostic laboratories in Scotland during the period 1988–99. Of 4491 isolates from hospitalized patients, 654 (64·7%) were from sputum, 79 (7·8%) from the nasopharynx and 278 (27·5%) from other superficial sites. The serogroups included in the 23-valent polysaccharide vaccine caused 96–9% of all non-invasive disease in all age groups. The 7-, 9-, and 11-valent conjugated vaccine serogroups were responsible for 87–94%, 85–93%, 74–81% and 75–84% of non-invasive disease respectively in age groups <2 years, [les ]5 years, [ges ]65 years and all ages. The coverage of non-susceptible penicillin and erythromycin non-invasive isolates was >99% and >95% with the 23-valent polysaccharide and 7–11-valent conjugate vaccines respectively. The eight most common serogroups were 23, 9, 6, 19, 14, 3, 15 and 11 (in descending order). The serogroups associated with antimicrobial resistance in non-invasive disease were similar to those found in invasive disease. The finding of a similar serogroup distribution in both invasive and non-invasive disease (regardless of the site of clinical isolate), is consistent with serogroups colonizing non-sterile sites and having the potential to invade. The availability of conjugated vaccines reinforces the importance of systematic surveillance to determine accurately and regularly the coverage of pneumococcal serogroups and types causing both invasive and non-invasive disease.

scholarly journals A Narrative Review of the W, X, Y, E, and NG of Meningococcal Disease: Emerging Capsular Groups, Pathotypes, and Global Control

2021 ◽  
Vol 9 (3) ◽  
pp. 519
Author(s):  
Yih-Ling Tzeng ◽  
David S. Stephens
Keyword(s):  
Meningococcal Disease ◽  
Capsular Polysaccharide ◽  
Clonal Complex ◽  
Invasive Disease ◽  
New Drugs ◽  
Sexually Transmitted ◽  
Meningococcal Vaccines ◽  
Containment Measures ◽  
Group B ◽  
Fatal Sepsis

Neisseria meningitidis, carried in the human nasopharynx asymptomatically by ~10% of the population, remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals. The epidemiology of invasive meningococcal disease (IMD) varies substantially by geography and over time and is now influenced by meningococcal vaccines and in 2020–2021 by COVID-19 pandemic containment measures. While 12 capsular groups, defined by capsular polysaccharide structures, can be expressed by N. meningitidis, groups A, B, and C historically caused most IMD. However, the use of mono-, bi-, and quadrivalent-polysaccharide-conjugate vaccines, the introduction of protein-based vaccines for group B, natural disease fluctuations, new drugs (e.g., eculizumab) that increase meningococcal susceptibility, changing transmission dynamics and meningococcal evolution are impacting the incidence of the capsular groups causing IMD. While the ability to spread and cause illness vary considerably, capsular groups W, X, and Y now cause significant IMD. In addition, group E and nongroupable meningococci have appeared as a cause of invasive disease, and a nongroupable N. meningitidis pathotype of the hypervirulent clonal complex 11 is causing sexually transmitted urethritis cases and outbreaks. Carriage and IMD of the previously “minor” N. meningitidis are reviewed and the need for polyvalent meningococcal vaccines emphasized.

scholarly journals Epidemiology of Invasive Group B Streptococcal Disease in Alberta, Canada, from 2003 to 2013

2016 ◽  
Vol 54 (7) ◽  
pp. 1774-1781 ◽  
Author(s):  
Areej Alhhazmi ◽  
Donna Hurteau ◽  
Gregory J. Tyrrell
Keyword(s):  
Capsular Polysaccharide ◽  
Late Onset ◽  
Disease Incidence ◽  
Invasive Disease ◽  
Erythromycin Resistance ◽  
Surveillance Period ◽  
Group B Streptococci ◽  
Screening Programs ◽  
Live Births ◽  
Group B

Group B streptococci (GBS) cause severe invasive disease in both neonates and adults. Understanding the epidemiology of GBS provides information that can include determining disease prevalence rates in defined populations and geographic regions, documenting the success of GBS screening programs, and understanding antimicrobial susceptibility patterns. In Alberta, only neonatal invasive GBS (iGBS) disease is notifiable to health authorities. We performed a surveillance study of iGBS in Alberta, Canada, from 2003 to 2013. Over the 11-year period, the disease incidence rate increased from a low of 3.92 cases/100,000 population to a high of 5.99 cases/100,000 population. The capsular polysaccharide serotypes (CPSs) found were CPS III (20.3%), CPS V (19.1%), CPS Ia (18.9%), CPS Ib (12.7%), CPS II (11.1%), CPS IV (6.3%), and nontypeable GBS (9.4%). Rates of early-onset disease (0 to 7 days) increased from 0.15 cases/1,000 live births (in 2003) to 0.34 cases/1,000 live births (in 2013). Rates of late-onset disease (>7 to 90 days) also rose, from 0.15 cases/1,000 live births (in 2003) to 0.39 cases/1,000 live births (in 2013). Alberta also experienced an increase in CPS IV isolates, from 2 cases (in 2003) to 24 cases (in 2013), of which the majority werehvgApositive (86.6%). The predominant sequence type (ST) in 2013 was ST459. Erythromycin resistance rose from 23.6% to 43.9% (in 2013). Clindamycin resistance also increased, from 12.2% to 32.5%. In summary, Alberta, Canada, has experienced an increase in GBS disease; the increase includes both neonatal and adult disease. CPS IV cases also notably increased during the surveillance period, as did resistance to erythromycin and clindamycin.

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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