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.

scholarly journals Immune Responses to Vi Capsular Polysaccharide Typhoid Vaccine in Children 2 to 16 Years Old in Karachi, Pakistan, and Kolkata, India

2014 ◽  
Vol 21 (5) ◽  
pp. 661-666 ◽  
Author(s):  
R. Leon Ochiai ◽  
M. Imran Khan ◽  
Sajid B. Soofi ◽  
Dipika Sur ◽  
Suman Kanungo ◽  
...  
Keyword(s):  
Hepatitis A ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Typhoid Vaccine ◽  
Igg Antibody ◽  
Vi Capsular Polysaccharide ◽  
Cluster Randomized ◽  
Antibody Levels

ABSTRACTThe geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P< 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P< 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.

scholarly journals Characterization of Citrobacter sp. line 328 as a source of Vi for a Vi-CRM197 glycoconjugate vaccine against Salmonella Typhi

2012 ◽  
Vol 6 (11) ◽  
pp. 763-773 ◽  
Author(s):  
Simona Rondini ◽  
Francesca Micoli ◽  
Luisa Lanzilao ◽  
Ivan Pisoni ◽  
Vito Di Cioccio ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Salmonella Typhi ◽  
Defined Medium ◽  
Industrial Scale ◽  
Scale Production ◽  
Populations At Risk ◽  
Vi Capsular Polysaccharide ◽  
High Yields ◽  
Antibody Levels

Introduction: Salmonella enterica serovar Typhi is the causative agent of typhoid fever with over 22 million cases and over 200,000 deaths reported annually. A vaccine is much needed for use in young children and the Novartis Vaccines Institute for Global Health (NVGH) is developing a conjugate vaccine which targets S. Typhi Vi capsular polysaccharide. Methodology: Here we describe a method suitable for industrial scale production of the Vi antigen based on expression by a Citrobacter line. We optimized the production of Vi by selecting a suitable Citrobacter strain (Citrobacter 328) that yields high and stable expression of Vi in chemically defined medium under industrial-scale fermentation conditions. Results: Vi-CRM197 made using Vi from Citrobacter 328 elicited high anti-Vi antibody levels in mice and rabbits. Conclusions: Citrobacter 328 is a suitable strain for production of Vi for conjugate anti-Typhi vaccines. Being a BSL-1 organism, which grows in defined medium and stably produces high yields of Vi, it offers excellent potential for safe production of inexpensive vaccines for populations at risk of typhoid fever.

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 A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women

1996 ◽  
Vol 117 (3) ◽  
pp. 519-524 ◽  
Author(s):  
R. Brugha ◽  
M. Ramsay ◽  
T. Forsey ◽  
D. Brown
Keyword(s):  
Immunosorbent Assay ◽  
Geometric Mean ◽  
Haemagglutination Inhibition ◽  
Enzyme Linked Immunosorbent Assay ◽  
History Of ◽  
Measles Vaccination ◽  
The Difference ◽  
Antibody Levels ◽  
Over Time

SummaryMaternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean litres were significantly higher in the unvaccinated than in the vaccinated mothers (P< 0·001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.

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 The Pneumococcal Polysaccharide-Tetanus Toxin Native C-Fragment Conjugate Vaccine: The Carrier Effect and Immunogenicity

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Rui Yu ◽  
Junjie Xu ◽  
Tao Hu ◽  
Wei Chen
Keyword(s):  
Tetanus Toxin ◽  
Capsular Polysaccharide ◽  
Low Cost ◽  
Culture Conditions ◽  
Carrier Protein ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines ◽  
Carrier Effect ◽  
Encapsulated Bacteria ◽  
Antibody Levels

The encapsulated bacteria, as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide. The capsular polysaccharide (PS), which could elicit a weak T cell-independent immune response, is a vital virulence determinant. One of the strategies to improve the PS-specific immunogenicity is to conjugate PS with a nontoxic carrier protein. Tetanus toxoid (TT) and CRM197 are the typical carrier proteins for the PS conjugate vaccines. TT is the inactivated tetanus toxin manipulated with formaldehyde, which suffers from the pollution from residual formaldehyde and the incomplete detoxification. CRM197 has the disadvantage of low-yield purification with the requirement of sophisticated culture conditions. Thus, a novel carrier protein without these disadvantages is highly required. The tetanus toxin native C-fragment (Hc) is safe, low-cost, and highly immunogenic with easy purification, which can act as a promising carrier protein. Pneumococcal serogroups 14 and 23F were major epidemic causes of pneumococcal infections. In the present study, the capsular PSs (PS14 and PS23F) were conjugated with Hc, TT, and CRM197, respectively. TT- and CRM197-based conjugates acted as controls for Hc-based conjugates (PS14-Hc and PS23F-Hc). The structural properties of Hc were not fundamentally changed after conjugated with PS. PS14-Hc and PS23F-Hc could potentiate sound PS-specific antibody levels comparable to the controls. Thus, Hc exhibited a practical carrier effect to help the pneumococcal conjugate vaccines perform good immunogenicities.

scholarly journals How Can the Typhoid Fever Surveillance in Africa and the Severe Typhoid Fever in Africa Programs Contribute to the Introduction of Typhoid Conjugate Vaccines?

2019 ◽  
Vol 69 (Supplement_6) ◽  
pp. S417-S421 ◽  
Author(s):  
Hyon Jin Jeon ◽  
Justin Im ◽  
Andrea Haselbeck ◽  
Marianne Holm ◽  
Raphaël Rakotozandrindrainy ◽  
...  
Keyword(s):  
High Risk ◽  
Typhoid Fever ◽  
Salmonella Typhi ◽  
World Health ◽  
Diagnostic Tools ◽  
Conjugate Vaccines ◽  
Mass Campaign ◽  
Seeking Behavior ◽  
Risk Areas ◽  
Health Organization

Abstract Background The World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar. Methods Data collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied. Results The Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture–based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease. Conclusions For Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

scholarly journals Enzyme-Linked Immunosorbent Assay for Measurement of Cytomegalovirus Glycoprotein B Antibody in Serum

2010 ◽  
Vol 17 (5) ◽  
pp. 836-839 ◽  
Author(s):  
Daniel J. Hackett ◽  
Changpin Zhang ◽  
Carla Stefanescu ◽  
Robert F. Pass
Keyword(s):  
Immunosorbent Assay ◽  
Geometric Mean ◽  
Mean Value ◽  
Glycoprotein B ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Negative Results ◽  
Wide Range ◽  
The Mean ◽  
Antibody Levels

ABSTRACT Measurement of antibody to cytomegalovirus (CMV) glycoprotein B (gB) is valuable in the assessment of the antibody response to infection and to gB-containing vaccines. For this purpose, an enzyme-linked immunosorbent assay (ELISA) with a recombinant CMV gB molecule as the antigen was evaluated. Sera from 168 anti-CMV IgG-positive and 100 seronegative subjects were used to evaluate the anti-gB antibody assay. A cutoff optical density (OD) that would distinguish gB antibody-positive from -negative sera was established. Titers of antibody to gB determined by endpoint dilution were compared with those calculated using regression analysis. The run-to-run and interoperator reproducibilities of results were measured. The mean OD + 5 standard deviations from 50 anti-CMV IgG antibody-negative sera (0.2472) was used as the cutoff between anti-gB antibody-positive and -negative results. All sera from 100 anti-CMV IgG-seronegative subjects were negative for antibody to gB. All but 1 of 168 sera from seropositive subjects were positive for antibody to gB. Observed antibody levels based on titration to the endpoint were very similar to results calculated using linear regression. The run-to-run consistency of endpoints was excellent, with 38 runs from one operator and 48 runs from another all giving results within 1 dilution of the mean value for each of three anti-CMV IgG antibody-positive serum pools. The geometric mean titer of antibody to gB for 99 sera from seropositive blood donors was 1/10,937. This ELISA gives accurate and reproducible results for the relative quantity of anti-CMV gB IgG in serum over a wide range of antibody levels.

scholarly journals Type-Specific Antibodies to Pneumococcal Capsular Polysaccharide Acquired either Naturally or after Vaccination with Prevenar in Children with Underlying Chronic or Recurrent Lung Diseases

2006 ◽  
Vol 13 (6) ◽  
pp. 665-670 ◽  
Author(s):  
David Navarro ◽  
Amparo Escribano ◽  
Laura Cebrián ◽  
Concepción Gimeno ◽  
Leonor García-Maset ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Capsular Polysaccharide ◽  
Serum Antibody ◽  
Invasive Disease ◽  
Significant Rise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Carrier Status ◽  
Specific Antibodies ◽  
Antibody Levels

ABSTRACT The antibody response to capsular polysaccharides of pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F elicited either naturally or after vaccination with Prevenar was investigated in a cohort of children (n = 163) with underlying chronic or recurrent lung diseases at risk of developing pneumococcal pneumonia and ultimately invasive disease. Serum concentrations of serotype-specific antibodies, as measured by enzyme-linked immunosorbent assay, in unvaccinated children (n = 88) were higher in nasopharyngeal carriers (n = 10) than in noncarriers (n = 78) both at baseline and during follow-up. However, the antibody levels depended on the serotype and age of the children. During the study period, 35% of unvaccinated noncarriers and 60% of unvaccinated carriers displayed serum antibodies to all serotypes above the reported WHO working group putative protective serum concentration against invasive disease (0.2 μg/ml). Overall, children vaccinated with Prevenar before enrollment (n = 61), irrespective of their carrier status, displayed significantly higher serum levels of antibodies to all serotypes than unvaccinated children. More than 85% of the vaccinated children had protective serum antibody concentrations at baseline; although antibody titers tended to decrease over time, the above-mentioned figure remained without change at the end of follow-up. The vaccine Prevenar elicited a significant rise in serum antibody concentrations against all serotypes in 14 children vaccinated at entry. All of these children acquired and maintained serum antibody levels of >0.2 μg/ml throughout the study (a mean of 13 months of follow-up). These data support the systematic use of the vaccine Prevenar in children with underlying chronic or recurrent lung diseases and stress the fact that a percentage of vaccinated children may need to be revaccinated in order to achieve protection against pneumococcal disease.

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