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Review
. 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

Laura Pöyhönen  1 , Jacinta Bustamante  1   2   3   4 , Jean-Laurent Casanova  1   2   3   5   6 , Emmanuelle Jouanguy  1   2   3 , Qian Zhang  7
Affiliations
Review

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

Laura Pöyhönen et al. J Clin Immunol. 2019 May.

Erratum in

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.

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Conflict of interest statement

Disclosures of Conflicts of Interest

The authors declare that they have no conflict of interest.

Figures

Figure 1:
Figure 1:. Schematic representation of type II IFN-related genetic disorders associated with BCG infections
In red, genes for which mutations have been associated with BCG infections. In black and white, genes not associated with BCG infections.
Figure 2:
Figure 2:. Schematic representation of type I and III IFN-related genetic disorders associated with vMeV infections
In red, genes for which mutations have been associated with vMeV infections. In black and white, genes not been associated with vMeV infections.
See this image and copyright information in PMC

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