Use and interpretation of diagnostic vaccination in primary immunodeficiency: A working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology

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A major diagnostic intervention in the consideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the application and interpretation of vaccination. Specifically, the antibody response to antigenic challenge with vaccines can provide substantive insight into the status of human immune function. There are numerous vaccines that are commonly used in healthy individuals, as well as others that are available for specialized applications. Both can potentially be used to facilitate consideration of PIDD. However, the application of vaccines and interpretation of antibody responses in this context are complex. These rely on consideration of numerous existing specific studies, interpolation of data from healthy populations, current diagnostic guidelines, and expert subspecialist practice. This document represents an attempt of a working group of the American Academy of Allergy, Asthma & Immunology to provide further guidance and synthesis in this use of vaccination for diagnostic purposes in consideration of PIDD, as well as to identify key areas for further research.

Section snippets

Use of common vaccines for measurement of humoral immune function

Summary Statement 1: The most commonly used vaccines for B-cell functional analysis are US Food and Drug Administration (FDA) approved and used worldwide in children to prevent communicable diseases. (Ia A)

Summary Statement 2: The diagnosis and treatment of common variable immunodeficiency (CVID) has traditionally included assessment of vaccine responses. (IIa B)

Summary Statement 3: There are 4 primary immunodeficiencies that largely depend on qualitative analysis of vaccination responses. (IV

Use of common vaccines for measurement of humoral immune function

A substantial number of vaccines are licensed for prophylactic use in the United States (Table I), and many are part of required or recommended vaccination series. Multiple PIDD diagnoses depend in part on the evaluation of the responses to these routine antigenic exposures. For direct guidance regarding the diagnosis of specific PIDDs, the reader is referred to the current (and any future) Joint Council of Allergy, Asthma & Immunology Practice Parameter on PIDDs.4 The following summary

Use of alternative vaccines and true neoantigens in evaluating defective humoral immunity

Summary Statement 46: Immunization with neoantigens can be used in the evaluation of specific antibody response in the setting of immunoglobulin replacement therapy. (III C)

The AAAAI’s “Practice parameter for the diagnosis and management of primary immune deficiency”4 recommends the use of standard childhood immunization for assessing antibody responses. Immunization with the neoantigen bacteriophage φX174 is an option in some centers for the evaluation of patients who are receiving

Variability in immunogenicity among currently available vaccines

Although rare, variability among vaccine lots does occur and can result in decreased immunogenicity and even vaccine failure. Conceivably, this could lead to inappropriate conclusions when vaccines are used in the assessment of immune competence. Ongoing efforts to standardize specifications for raw materials, production facilities, manufacturing processes, and control testing of vaccines are robust and imperative. General aspects pertaining to potential variability, as well as issues specific

Conclusion

The use of vaccine responses as a diagnostic tool is firmly established for the evaluation of patients undergoing immunologic evaluation. They are frequently used in the context of providing a diagnosis or for justifying a particular therapeutic intervention. However, it is important to recognize that a knowledge gap exists regarding the issue of the different titer responses associated with the specific sequence of vaccination formulations (eg, PCV before PPV or vice versa). The effect

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    Publication of this article was supported by CSL Behring.

    Disclosure of potential conflict of interest: J. S. Orange has received consultancy fees from Baxter Bioscience, Grifols, Octapharma USA, CSL Behring, IBT Reference Laboratories, and Cangene; has received lecture fees from Baxter Bioscience; and receives royalties from UpToDate. M. Ballow has received consulting fees from Baxter, CSL Behring, Grifols; has received fees for participation in review activities from Green Cross DSMB; has received legal fees to review a case; has received lecture fees from Baxter, CSL Behring, and the ACAAI; and has received payment for manuscript preparation from Baxter. E. R. Stiehm has received consultancy fees from UpToDate; is employed by Vela; has provided expert witness testimony on the topic of vaccine adverse effects; has received an unrestricted donation to Dr. Roger Kobayashi Allergy and Immunology Associates of Omaha for travel expenses; and has received travel expenses from the US Immune Deficiency Foundation and March of Dimes. Z. K. Ballas has received research support from Talecris, VA, and the National Institutes of Health (NIH); receives royalties from UpToDate; and has served as a member of the AAAAI Board of Directors. M. De La Morena has received research support from the Jeffrey Modell Foundation. D. Kumararatne has received research support from NIHR, UK; has received consultancy fees from Viropharma; has received lecture payments from Baxter; and has received travel funds from CSL Behring. S. McGhee has received lecture fees from Baxter. E. E. Perez has received consultancy fees from Baxter and CSL Behring; is employed by the University of South Florida; and has received payment for the development of educational presentations from Baxter. J. Raasch has received lecture fees from Baxter and CSL Behring and has received payment for the development of educational presentations from Baxter. H. Schroeder has received research support from the NIAID, NABI Pharmaceuticals, and Green Cross Pharmaceuticals; has received lecture fees from the AAAAI and NABI Pharmaceuticals; and has received royalties from Elsevier as the editor of Clinical Immunology: Principles and Practices. C. Seroogy has received consultancy fees from UpToDate; is employed by the University of Wisconsin; and has received research support from Midwest Athletes Against Childhood Cancer and the NIH. A. Huissoon has served on the Advisory Boards for Biotest, Shire, Swedish Orphan Biovitrum, and Meda; has received lecture fees from GlaxoSmithKline; holds shares in GlaxoSmithKline; has received travel expenses from CSL Behring; and has organized meetings that have been funded by The Binding Site, Ltd. The rest of the authors have declared that they have no relevant conflicts of interest.

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