scholarly journals Avidity of the Immunoglobulin G Response to a Neisseria meningitidis Group C Polysaccharide Conjugate Vaccine as Measured by Inhibition and Chaotropic Enzyme-Linked Immunosorbent Assays

2007 ◽  
Vol 14 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Shannon L. Harris ◽  
How Tsao ◽  
Lindsey Ashton ◽  
David Goldblatt ◽  
Philip Fernsten
Keyword(s):  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Immunization ◽  
Individual Subject ◽  
Antibody Avidity ◽  
Booster Immunization ◽  
Immunization Series

ABSTRACT Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (KD s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) KD was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM KD , 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the KD , reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions.

scholarly journals Effect of O Acetylation of Neisseria meningitidis Serogroup A Capsular Polysaccharide on Development of Functional Immune Responses

2002 ◽  
Vol 70 (7) ◽  
pp. 3707-3713 ◽  
Author(s):  
David S. Berry ◽  
Freyja Lynn ◽  
Che-Hung Lee ◽  
Carl E. Frasch ◽  
Margaret C. Bash
Keyword(s):  
Immune Responses ◽  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Essential Role ◽  
Capsular Polysaccharide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dramatic Reduction ◽  
Mouse Immunization ◽  
Human Sera ◽  
Inhibition Studies

ABSTRACT The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of murine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that O acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection.

Persistence of Antibody Following Immunization of Children With Groups A and C Meningococcal Polysaccharide Vaccines

PEDIATRICS ◽  
1977 ◽  
Vol 60 (5) ◽  
pp. 673-680 ◽  
Author(s):  
Martha L. Lepow ◽  
Irving Goldschneider ◽  
Ronald Gold ◽  
Martin Randolph ◽  
Emil C. Gotschlich
Keyword(s):  
Meningococcal Disease ◽  
Geometric Mean ◽  
Routine Immunization ◽  
Antibody Concentration ◽  
Primary Immunization ◽  
Booster Immunization ◽  
Young Infants ◽  
Group A ◽  
One Year ◽  
Control Of Epidemics

Persistence of antibody following immunization with groups A and C meningococcal polysaccharides was studied in two groups of children. Cohort 1 (20 children, 2 to 11 years of age) received two doses of A vaccine three years apart; cohort 2 (1,345 children, 6 to 8 years of age) received A or C vaccine initially and the heterologous vaccine one year later. No significant reactions were observed. Geometric mean anti-A concentrations one month after primary and booster immunizations in cohort 1 were 8.77 and 13.08 µg/ml, respectively. Mean anti-A concentration declined 32% one year after booster immunization, but then stabilized. Mean anti-A and anti-C concentrations in cohort 2 were 9.35 and 9.12 µg/ml, respectively, one month after primary immunization. Mean anti-A concentration declined to 5.54 and 3.62 µg/ml while anti-C levels fell to 2.35 and 1.47 µg/ml one and four years after immunization. The proportion of children in cohort 2 with ≥ 2.0 µg/ml of anti-A and anti-C four years after immunization were 80% and 40%, respectively. An antibody concentration ≥2.0 µg/ml has been associated with protection against meningococcal disease. The results suggest that routine immunization of young infants with group A vaccine may result in long-lasting immunity. The usefulness of the presently available group C vaccine appears to be limited to the control of epidemics.

scholarly journals Randomized, Controlled Trial of a 13-Valent Pneumococcal Conjugate Vaccine Administered Concomitantly with an Influenza Vaccine in Healthy Adults

2012 ◽  
Vol 19 (8) ◽  
pp. 1296-1303 ◽  
Author(s):  
Robert W. Frenck ◽  
Alejandra Gurtman ◽  
John Rubino ◽  
William Smith ◽  
Martin van Cleeff ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Group 2 ◽  
Group 1

ABSTRACTA randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n= 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessedpost hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ≥4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%;P< 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances.

scholarly journals The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines

2011 ◽  
Vol 18 (5) ◽  
pp. 730-735 ◽  
Author(s):  
Vu Dinh Thiem ◽  
Feng-Ying C. Lin ◽  
Do Gia Canh ◽  
Nguyen Hong Son ◽  
Dang Duc Anh ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Type B ◽  
Protective Level ◽  
Content Type ◽  
Expanded Program On Immunization ◽  
Routine Infant

ABSTRACTTyphoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) ofSalmonella entericaserovar Typhi (Vi) bound to recombinant exoprotein A ofPseudomonas aeruginosa(Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA orHaemophilus influenzaetype b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

scholarly journals Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age

2009 ◽  
Vol 17 (3) ◽  
pp. 311-316 ◽  
Author(s):  
S. J. Moss ◽  
A. C. Fenton ◽  
J. Toomey ◽  
A. Grainger ◽  
R. Borrow ◽  
...  
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Haemophilus Influenzae Type ◽  
Type B ◽  
Term Infants ◽  
Meningococcal Group ◽  
Pneumococcal Serotype

ABSTRACT The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7.

scholarly journals Analysis of Human Serum Immunoglobulin G against O-Acetyl-Positive and O-Acetyl-Negative Serogroup W135 Meningococcal Capsular Polysaccharide

2005 ◽  
Vol 12 (5) ◽  
pp. 586-592 ◽  
Author(s):  
Peter C. Giardina ◽  
Emma Longworth ◽  
Renee E. Evans-Johnson ◽  
Michaelene L. Bessette ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Capsular Polysaccharide ◽  
Solid Phase ◽  
Geometric Mean ◽  
Serum Antibody ◽  
Fluid Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Titers ◽  
The Impact

ABSTRACT The capsular polysaccharide of Neisseria meningitidis serogroup W135 is expressed in both O-acetyl-positive (OA+) and O-acetyl-negative (OA−) forms. This study investigates the impact of OA status (OA+ versus OA−) on serological measurements of anti-W135 immunoglobulin G (IgG) antibodies in immunized adults. W135-specific serum antibody assignments were made for 28 postimmunization sera from adults by enzyme-linked immunosorbent assay using the meningococcal standard reference serum CDC1992. The established IgG concentration in micrograms per milliliter ([IgG]μg/ml) for CDC1992 against OA+ antigen (16.2 μg/ml) was used as a reference to assign a concentration of 10.13 μg/ml IgG against OA− antigen by cross-standardization. Overall, the IgG assignments for these sera were higher against OA+ antigen (geometric mean concentration [GMC] = 7.16 μg/ml) than against OA− antigen (GMC = 2.84 μg/ml). However, seven sera showed higher specific [IgG]μg/ml values against the OA+ antigen than against the OA− antigen. These sera were also distinguished by the inability of fluid-phase OA− antigen to compete for antibody binding to OA+ solid-phase antigen. Although there was no overall difference in functional activity measured by complement-mediated serum bactericidal assay (SBA) against OA+ and OA− target bacteria (geometric mean titers of 9,642 and 9,045, respectively), three serum specimens showed a large difference in SBA antibody titers against OA+ versus OA− W135 target bacteria, which may reflect different epitope specificities for these sera. Our data indicate that, for some sera, the agreement in anti-OA+ versus anti-OA− W135 IgG assignments is serum specific and does not reflect the functional (killing) activity in vitro.

scholarly journals A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacopo Enotarpi ◽  
Marta Tontini ◽  
Cristiana Balocchi ◽  
Daan van der Es ◽  
Ludovic Auberger ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Shelf Life ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Antibody Binding ◽  
Liquid Formulation ◽  
In Vivo Testing ◽  
Protective Antibodies ◽  
Polyclonal Serum

AbstractNeisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.

scholarly journals Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid Fever in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

1999 ◽  
Vol 67 (11) ◽  
pp. 5806-5810 ◽  
Author(s):  
Zuzana Kossaczka ◽  
Feng-Ying C. Lin ◽  
Vô Anh Ho ◽  
Nguyen Thi Thanh Thuy ◽  
Phan Van Bay ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Salmonella Typhi ◽  
Enzyme Linked Immunosorbent Assay ◽  
Conjugate Vaccines ◽  
Local Reactions ◽  
Antibody Levels ◽  
Igg Level

ABSTRACT The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using eitherN-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA1) or adipic acid dihydrazide (ADH; Vi-rEPA2) as linkers. None of the recipients experienced a temperature of >38.5°C or significant local reactions. One injection of Vi-rEPA2 into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA2, Vi-rEPA1, and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA2, Vi-rEPA1, and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2); all were higher than the preinjection levels (P = 0.0001). Vi-rEPA2 also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA2 elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA1(P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA2 and from 28.9 to 83.0 EU for Vi-rEPA1. At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA2 and 12.8 versus 0.33 for Vi-rEPA1; P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA2 in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA2conjugate warrant further investigation.

Neonatal Immunization: Response to Haemophilus influenzae Type b-Tetanus Toxoid Conjugate Vaccine

PEDIATRICS ◽  
1995 ◽  
Vol 95 (6) ◽  
pp. 815-822
Author(s):  
Sari Kurikka ◽  
Helena Käyhty ◽  
Heikki Peltola ◽  
Leena Saarinen ◽  
Juhani Eskola ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Natural Decay

Objective. To study the immunogenicity and tolerability of Haemophilus influenzae type b (Hib) conjugate vaccine administered in the neonatal period. Design. Hib capsular polysaccharide (PS)-tetanus toxoid conjugate vaccine (PRP-T) was given to 120 neonates at 2 days of age, followed by PRP-T or the Hib PS vaccine at 4 months and a PRP-T booster at 14 months. Their anti-Hib PS concentrations were compared with those in children receiving PRP-T at 2 and 4 months or at 4 months. Results. No serious adverse reactions were noted. The geometric mean concentration of anti-Hib PS at the age of 2 days was 0.34 µg/mL and at 4 months was 0.12 µg/mL. This was significantly more than the concentration in unimmunized infants at this age and 3.5 times more than expected, taking into account the natural decay of transplacentally acquired antibodies. Such a response was not seen in infants with a high (greater than 3.0 µg/mL) neonatal antibody concentration. The PRP-T vaccine given at 4 months elicited an antibody response in all infants and Hib PS in 62%, indicating immunologic priming. At 14 months a higher percentage of the infants who had received PRP-T at 2 days and 4 months than of those who had received PRP-T at 4 months only had anti-Hib PS concentrations greater than 0.15 µg/mL. All infants responded well to the booster at 14 months. There was no evidence of immunologic tolerance. Conclusions. Neonatal immunization with PRP-T was safe and well tolerated in Finnish infants, and it would be worthwhile to further study its effects in higher risk populations.

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