Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan;23(1):e34-e42.
doi: 10.1016/S1473-3099(22)00498-4. Epub 2022 Aug 26.

Beneficial non-specific effects of live vaccines against COVID-19 and other unrelated infections

Peter Aaby  1 , Mihai G Netea  2 , Christine S Benn  3
Affiliations
Review

Beneficial non-specific effects of live vaccines against COVID-19 and other unrelated infections

Peter Aaby et al. Lancet Infect Dis. 2023 Jan.

Abstract

Live attenuated vaccines could have beneficial, non-specific effects of protecting against vaccine-unrelated infections, such as BCG protecting against respiratory infection. During the COVID-19 pandemic, testing of these effects against COVID-19 was of interest to the pandemic control programme. Non-specific effects occur due to the broad effects of specific live attenuated vaccines on the host immune system, relying on heterologous lymphocyte responses and induction of trained immunity. Knowledge of non-specific effects has been developed in randomised controlled trials and observational studies with children, but examining of whether the same principles apply to adults and older adults was of interest to researchers during the pandemic. In this Personal View, we aim to define a framework for the analysis of non-specific effects of live attenuated vaccines against vaccine-unrelated infections with pandemic potential using several important concepts. First, study endpoints should prioritise severity of infection and overall patient health rather than incidence of infection only (eg, although several trials found no protection of the BCG vaccine against COVID-19 infection, it is associated with lower overall mortality than placebo). Second, revaccination of an individual with the same live attenuated vaccine could be the most effective strategy against vaccine-unrelated infections. Third, coadministration of several live attenuated vaccines might enhance beneficial non-specific effects. Fourth, the sequence of vaccine administration matters; the live attenuated vaccine should be the last vaccine administered before exposure to the pandemic infection and non-live vaccines should not be administered afterwards. Fifth, live attenuated vaccines could modify the immune response to specific COVID-19 vaccines. Finally, non-specific effects of live attenuated vaccines should always be analysed with subgroup analysis by sex of individuals receiving the vaccines.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests We declare no competing interests.

Figures

Figure
Figure
Non-specific effects of vaccines are affected by factors affecting the general immune system
See this image and copyright information in PMC

References

    1. Benn CS, Fisker AB, Rieckmann A, Sørup S, Aaby P. Vaccinology: time to change the paradigm? Lancet Infect Dis. 2020;20:e274–e283. - PubMed
    1. Aaby P, Martins CL, Garly ML, et al. Non-specific effects of standard measles vaccine at 4·5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ. 2010;341 - PMC - PubMed
    1. Lund N, Andersen A, Hansen AS, et al. The effect of oral polio vaccine at birth on infant mortality: a randomized trial. Clin Infect Dis. 2015;61:1504–1511. - PMC - PubMed
    1. Aaby P, Roth A, Ravn H, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011;204:245–252. - PubMed
    1. Biering-Sørensen S, Aaby P, Lund N, et al. Early BCG-Denmark and neonatal mortality among infants weighing <2500 g: a randomized controlled trial. Clin Infect Dis. 2017;65:1183–1190. - PMC - PubMed