Journal of Clinical Immunology

, Volume 37, Issue 5, pp 427–433 | Cite as

The Use of Salmonella Typhim Vaccine to Diagnose Antibody Deficiency

  • Mary T. Bausch-Jurken
  • James W. Verbsky
  • Katherine A. Gonzaga
  • Nancy P. Elms
  • Mary K. Hintermeyer
  • Stephen B. Gauld
  • John M. RoutesEmail author
Original Article



The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA.


We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy.


Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin.


This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.


Immunodeficiency humoral immunodeficiency vaccination response S. Typhim vaccination immunoglobulin replacement 


Author’s Contributions

N.E. performed the ELISAs; all other authors contributed to the design of the study, identification, and recruitment of the subjects and chart review. J.R., J.V., and M.B. contributed equally to the writing of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

John Routes, MD, received support from CSL Behring as an independent contractor for activities unrelated to the topic of this manuscript or study. The authors declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Institutional Review Board of Children’s Hospital of Wisconsin for the duration of the study from July, 2010 through December, 2016. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendment or comparable ethical standards.

Informed Consent

Written informed consent was obtained from all individual participants or their guardians included in this study.

Supplementary material

10875_2017_406_MOESM1_ESM.pptx (105 kb)
ESM 1 (PPTX 104 kb).
10875_2017_406_MOESM2_ESM.docx (49 kb)
ESM 2 (DOCX 49 kb).


  1. 1.
    Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4:38–59.CrossRefPubMedGoogle Scholar
  2. 2.
    Ferry BL, Misbah SA, Stephens P, Sherrell Z, Lythgoe H, Bateman E, et al. Development of an anti-salmonella typhi vi ELISA: assessment of immunocompetence in healthy donors. Clin Exp Immunol. 2004;136:297–303.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bousfiha A, Jeddane L, Al-Herz W, Ailal F, Casanova JL, Chatila T, et al. The 2015 IUIS phenotypic classification for primary immunodeficiencies. J Allergy Clin Immunol. 2015;35:727–38.Google Scholar
  4. 4.
    Sánchez-Ramón S, de Gracia J, García-Alonso AM, Molina JR, Melero J, de Andrés A, et al. Multicenter study for the evaluation of the antibody response against salmonella typhi vi vaccination (EMPATHY) for the diagnosis of anti-polysaccharide antibody production deficiency in patients with primary immunodeficiency. Clin Immunol. 2016;169:80–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Mary T. Bausch-Jurken
    • 1
  • James W. Verbsky
    • 2
  • Katherine A. Gonzaga
    • 1
  • Nancy P. Elms
    • 1
  • Mary K. Hintermeyer
    • 3
  • Stephen B. Gauld
    • 4
  • John M. Routes
    • 1
    Email author
  1. 1.Department of Pediatrics, Divisions of Allergy and Clinical ImmunologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of Pediatrics, Division of RheumatologyMedical College of WisconsinMilwaukeeUSA
  3. 3.Children’s Hospital of WisconsinMilwaukeeUSA
  4. 4.Immunology/DermatologyNorth ChicagoUSA

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