Work

Human genetics of susceptibility to live-attenuated viral vaccines

Year: 2026

Type: review

Abstract: Alongside the development of antibiotics, vaccination is the medical innovation with arguably the greatest impact on human health. Testament to its success is the eradication of infectious diseases, such as smallpox, that devastated human populations for almost 4000 years. Live-attenuated vaccines (LAV), which retain the capacity for infection and replication, were the first to be developed and remain highly efficacious, underpinning successful human vaccination campaigns (e.g. polio virus, measles virus, yellow fever virus). The cost of this success is the capacity of LAVs to cause disease in a small proportion of recipients, typically owing to overt or previously unappreciated immunodeficiency. From the careful investigation of such rare events, major clinical and scientific lessons about human antiviral immunity have been drawn. Here, we review features of pathogenic LAV dissemination, which continue to inform our understanding of critical steps in the immune control of LAVs. We discuss recent data on specific variants identified in geographically isolated populations and reflect on more common phenocopies of these monogenic defects, with potential implications for vaccine practice and policy. Collectively, these insights may inform approaches to the growing population of individuals rendered more vulnerable to LAVs by aging, multimorbidity or medical intervention. They also serve to highlight the clinical need for therapeutic strategies to combat pathogenic LAV dissemination. • Disease secondary to LAV dissemination heralds inborn or acquired immunodeficiency. • The spectrum of LAV disease provides insight into human antiviral immunity. • T cell defects result in broad susceptibility to LAVs. • Defects of innate interferon immunity confer vulnerability to a range of LAVs. • Defects of type I interferon immunity are more common than initially anticipated.

Source: Current Opinion in Virology

DOI: 10.1016/j.coviro.2026.101512

Authors: Phoebe Hazenberg, Christopher JA Duncan

Institutions: Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Hospital, Newcastle University

Language: English

Topic: Immunodeficiency and Autoimmune Disorders

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,690