Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly

Cell. 2020 Oct 15;183(2):315-323.e9. doi: 10.1016/j.cell.2020.08.051. | PubMed

Evangelos J Giamarellos-Bourboulis¹, Maria Tsilika², Simone Moorlag³, Nikolaos Antonakos², Antigone Kotsaki², Jorge Domínguez-Andrés³, Evdoxia Kyriazopoulou², Theologia Gkavogianni², Maria-Evangelia Adami², Georgia Damoraki², Panagiotis Koufargyris², Athanassios Karageorgos², Amalia Bolanou², Hans Koenen⁴, Reinout van Crevel³, Dionyssia-Irene Droggiti², George Renieris², Antonios Papadopoulos², Mihai G Netea⁵

1. 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece. Electronic address: egiamarel@med.uoa.gr.
2. 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece.
3. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 Nijmegen, the Netherlands.
4. Department of Laboratory Medicine, Radboud University Medical Center, 6500 Nijmegen, the Netherlands.
5. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.

Abstract

BCG vaccination in children protects against heterologous infections and improves survival independently of tuberculosis prevention. The phase III ACTIVATE trial assessed whether BCG has similar effects in the elderly. In this double-blind, randomized trial, elderly patients (n = 198) received BCG or placebo vaccine at hospital discharge and were followed for 12 months for new infections. At interim analysis, BCG vaccination significantly increased the time to first infection (median 16 weeks compared to 11 weeks after placebo). The incidence of new infections was 42.3% (95% CIs 31.9%-53.4%) after placebo vaccination and 25.0% (95% CIs 16.4%-36.1%) after BCG vaccination; most of the protection was against respiratory tract infections of probable viral origin (hazard ratio 0.21, p = 0.013). No difference in the frequency of adverse effects was found. Data show that BCG vaccination is safe and can protect the elderly against infections. Larger studies are needed to assess protection against respiratory infections, including COVID-19 (ClinicalTrials.gov NCT03296423).

Presented By Evangelos Giamarellos-Bourboulis