Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 39, Issue 4, Pages 376-390Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-019-00642-3
Keywords
Live-attenuated vaccine; primary immunodeficiency; inborn error of immunity; BCG; OPV; MMR; ORV; IFN
Categories
Funding
- National Institute of Allergy and Infectious Diseases [R37AI095983]
- National Vaccine Program Office of the US Department of Health and Human Service [VSRNV000006]
- St. Giles Foundation
- Rockefeller University
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- French National Research Agency under the Investments for the future program [ANR-10-IAHU-01]
- ANR-GENMSMD [ANR-16-CE17-0005-01]
- ECOS-NORD [C19S01-63407]
- SRC2017
- Institute National de la Sante et de la Recherche Medicale (INSERM), Paris Descartes University
- Agence Nationale de la Recherche (ANR) [ANR-16-CE17-0005] Funding Source: Agence Nationale de la Recherche (ANR)
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Live-attenuated vaccines (LAVs) can protect humans against 12 viral and three bacterial diseases. By definition, any clinical infection caused by a LAV that is sufficiently severe to require medical intervention attests to an inherited or acquired immunodeficiency that must be diagnosed or identified. Self-healing infections can also result from milder forms of immunodeficiency. We review here the inherited forms of immunodeficiency underlying severe infections of LAVs. Inborn errors of immunity (IEIs) underlying bacille Calmette-Guerin (BCG), oral poliovirus (OPV), vaccine measles virus (vMeV), and oral rotavirus vaccine (ORV) disease have been described from 1951, 1963, 1966, and 2009 onward, respectively. For each of these four LAVs, the underlying IEIs show immunological homogeneity despite genetic heterogeneity. Specifically, BCG disease is due to inborn errors of IFN-gamma immunity, OPV disease to inborn errors of B cell immunity, vMeV disease to inborn errors of IFN-alpha/beta and IFN-lambda immunity, and ORV disease to adaptive immunity. Severe reactions to the other 11 LAVs have been described yet remain idiopathic, in the absence of known underlying inherited or acquired immunodeficiencies, and are warranted to be the focus of research efforts. The study of IEIs underlying life-threatening LAV infections is clinically important for the affected patients and their families, as well as immunologically, for the study of the molecular and cellular basis of host defense against both attenuated and parental pathogens.
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