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J Clin Immunol. 2019 May;39(4):376-390. doi: 10.1007/s10875-019-00642-3. Epub 2019 May 23.

Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity.

Author information

1
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
2
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.
3
Imagine Institute, Paris Descartes University, Paris, France.
4
Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France.
5
Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
6
Howard Hughes Medical Institute, New York, NY, USA.
7
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. qzhang02@mail.rockefeller.edu.

Abstract

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-Guérin (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-γ immunity, OPV disease to inborn errors of B cell immunity, vMeV disease to inborn errors of IFN-α/β and IFN-λ 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.

KEYWORDS:

BCG; IFN; Live-attenuated vaccine; MMR; OPV; ORV; inborn error of immunity; primary immunodeficiency

PMID:
31123910
DOI:
10.1007/s10875-019-00642-3

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