scholarly journals A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination

2021 ◽  
Vol 9 (7) ◽  
pp. 1394
Author(s):  
Elizabeth Jones ◽  
Celina Jin ◽  
Lisa Stockdale ◽  
Christina Dold ◽  
Andrew J. Pollard ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Conjugate Vaccines ◽  
Serum Bactericidal Activity ◽  
Iga Antibodies ◽  
Protection Against Infection ◽  
Infection Study

Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response to Vi conjugate or Vi plain polysaccharide vaccination are important but there are no definitive protective titre thresholds. We adapted a luminescence-based serum bactericidal activity (SBA) for use with S. Typhi and assessed whether bactericidal antibodies induced by either Vi tetanus toxoid conjugate (Vi-TT) or Vi plain polysaccharide (Vi-PS) were associated with protection in a controlled human infection model of typhoid fever. Both Vi-PS and Vi-TT induced significant increase in SBA titre after 28 days (Vi-PS; p < 0.0001, Vi-TT; p = 0.003), however higher SBA titre at the point of challenge did not correlate with protection from infection or reduced symptom severity. We cannot eliminate the role of SBA as part of a multifactorial immune response which protects against infection, however, our results do not support a strong role for SBA as a mechanism of Vi vaccine mediated protection in the CHIM setting.

scholarly journals Vi-specific serological correlates of protection for typhoid fever

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Celina Jin ◽  
Jennifer Hill ◽  
Bronwyn M. Gunn ◽  
Wen-Han Yu ◽  
Lindsay C. Dahora ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Multivariate Analyses ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Functional Responses ◽  
Conjugate Vaccines ◽  
Correlates Of Protection ◽  
Study Participants ◽  
Vaccine Availability ◽  
Infection Study

Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates of protection using samples obtained from participants enrolled in an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) vaccines and were subsequently challenged with Salmonella Typhi bacteria. Multivariate analyses identified distinct protective signatures for Vi-TT and Vi-PS vaccines in addition to shared features that predicted protection across both groups. Vi IgA quantity and avidity correlated with protection from S. Typhi infection, whereas higher fold increases in Vi IgG responses were associated with reduced disease severity. Targeted antibody-mediated functional responses, particularly neutrophil phagocytosis, were also identified as important components of the protective signature. These humoral markers could be used to evaluate and develop efficacious Vi-conjugate vaccines and assist with accelerating vaccine availability to typhoid-endemic regions.

scholarly journals IgA and IgG1 Specific to Vi Polysaccharide of Salmonella Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model

2019 ◽  
Vol 10 ◽  
Author(s):  
Lindsay C. Dahora ◽  
Celina Jin ◽  
Rachel L. Spreng ◽  
Frederick Feely ◽  
Ryan Mathura ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model

scholarly journals Salmonella Typhi Bactericidal Antibodies Reduce Disease Severity but Do Not Protect against Typhoid Fever in a Controlled Human Infection Model

2018 ◽  
Vol 8 ◽  
Author(s):  
Helene B. Juel ◽  
Helena B. Thomaides-Brears ◽  
Thomas C. Darton ◽  
Claire Jones ◽  
Elizabeth Jones ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Disease Severity ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Reduce Disease Severity

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 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 The Role of the Mosquito in a Dengue Human Infection Model

2014 ◽  
Vol 209 (suppl 2) ◽  
pp. S71-S78 ◽  
Author(s):  
C. N. Mores ◽  
R. C. Christofferson ◽  
S. A. Davidson
Keyword(s):  
Human Infection ◽  
Infection Model

Role of Shamanaushadhi in Typhoid Fever – An Observational Clinical Study

2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Saurabh Parauha ◽  
M. A. Hullur ◽  
Prashanth. A. S.
Keyword(s):  
Clinical Study ◽  
Typhoid Fever ◽  
Blood Stream ◽  
Salmonella Typhi ◽  
Acute Illness ◽  
Widal Test ◽  
Risk Area ◽  
High Risk Area

Typhoid fever is an acute illness associated with fever that is most often caused by the Salmonella typhi bacteria. Once the bacteria is ingested it quickly multiplies within the stomach, liver or gall bladder and finally enters the blood stream causing symptoms like fever, headache etc. these cases as of 2010 caused about 190000 deaths up from 137000 in 1990 in whole world, India, Pakistan and Egypt are also known high risk area for developing this disease. A clinical study comprising of 15 patients of either sex attending OPD clinic of AMVH Hubli and presenting with clinical manifestation of Typhoid confirmed by Widal test were selected for observational study. All the patients received Sanjivani Vati 2 tab. bid with Kiratadisapta Kashaya (20 ml) twice daily after food. It was given for 21 days and follow up period was of 1 month with weekly visit. From the result obtained we can conclude that therapy with this Ayurvedic combination of drugs shown significant relief (p less than 0.001) in symptoms after 21 days of treatment.

scholarly journals An Outpatient, Ambulant-Design, Controlled Human Infection Model Using Escalating Doses of Salmonella Typhi Challenge Delivered in Sodium Bicarbonate Solution

2014 ◽  
Vol 58 (9) ◽  
pp. 1230-1240 ◽  
Author(s):  
Claire S. Waddington ◽  
Thomas C. Darton ◽  
Claire Jones ◽  
Kathryn Haworth ◽  
Anna Peters ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Sodium Bicarbonate Solution ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model
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