The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines

PLoS One. 2022 Jun 3;17(6):e0268042. doi: 10.1371/journal.pone.0268042. eCollection 2022.

Abstract

Background: With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination.

Methods: Participants who received influenza vaccine alone (Influenza group) were compared with those who also received BCG-Denmark vaccine in the contralateral arm (Influenza+BCG group). Data on the influenza vaccination site were collected using serial questionnaires and active follow-up for 3 months post vaccination.

Results: Of 1351 participants in the Influenza+BCG group and 1418 participants in the Influenza group, 2615 (94%) provided influenza vaccine safety data. There was no significant difference in the proportion of participants with any local adverse reaction between the Influenza+BCG group and the Influenza group (918/1293 [71.0%] versus (906/1322 [68.5%], p = 0.17). The proportion of participants reporting any pain, erythema and tenderness at the influenza vaccination site were similar in both groups. Swelling was less frequent (81/1293 [6.3%] versus 119/1322 (9.0%), p = 0.01) and the maximal diameter of erythema was smaller (mean 1.8 cm [SD 2.0] versus 3.0 cm [SD 2.5], p<0.001) in the Influenza+BCG group. Sixteen participants reported serious adverse events: 9 participants in the Influenza+BCG group and 7 in the Influenza group.

Conclusions: Adverse events following influenza vaccination are not increased when BCG is co-administered.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BCG Vaccine* / adverse effects
  • Humans
  • Influenza Vaccines* / adverse effects
  • Influenza, Human* / prevention & control
  • Vaccination / adverse effects

Substances

  • BCG Vaccine
  • Influenza Vaccines

Grants and funding

The Murdoch Children’s Research Institute (MCRI) leads the BRACE trial across 36 sites in five countries. It is supported by the Victorian Government’s Operational Infrastructure Support Program. PV is supported by the Australian Government Research Training Program Scholarship provided by the Australian Commonwealth Government and the University of Melbourne, and a MCRI PhD Top Up Scholarship. LFP is supported by the Swiss National Science Foundation [Early Postdoc Mobility Grant, P2GEP3_178155]. NC is supported by a National Health and Medical Research Council Investigator Grant [GNT1197117]. The BRACE trial is supported by the Bill & Melinda Gates Foundation [INV-017302], the Minderoo Foundation [COV-001], Sarah and Lachlan Murdoch, the Royal Children’s Hospital Foundation [2020-1263 BRACE Trial], Health Services Union NSW, the Peter Sowerby Foundation, the Ministry of Health Government of South Australia, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare and individual donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.