Related Experiment Video
Updated: Jun 19, 2025

Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Immune cell population dynamics following neonatal BCG vaccination and aerosol BCG revaccination in rhesus macaques
Laura Sibley1, Charlotte Sarfas1, Alexandra L Morrison1
1UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Insights
BCG vaccination in infant macaques did not alter immune cell development but induced short-term antigen-specific responses. Long-term revaccination in adulthood showed potential for trained innate immunity, impacting future immune responses.
Area of Science:
- Immunology
- Vaccinology
Background:
- Bacille Calmette-Guérin (BCG) vaccine efficacy wanes over time.
- Infant and adult immune systems differ, potentially affecting vaccine effectiveness.
Purpose of the Study:
- To investigate the impact of early-life BCG vaccination on immune cell populations in infant rhesus macaques.
- To assess the long-term effects of infant BCG vaccination on immune responses to revaccination in adulthood.
Main Methods:
- 34 infant rhesus macaques were vaccinated with BCG and monitored for 88 weeks.
- Blood samples were analyzed for immune cell population changes.
- A pilot study involved BCG revaccination in adult macaques previously vaccinated as infants.
Main Results:
- BCG vaccination did not significantly alter immune cell composition or perturb normal development in infants.
- Infants exhibited higher CD4+ T-cells, Tregs, and NK cells compared to adults.
- Antigen-specific IFNγ responses in infants were detectable for 36 weeks post-vaccination.
- Adult revaccination induced increased PPD-specific IFNγ and cytokine secretion, suggesting trained innate immunity.
Conclusions:
- Early-life BCG vaccination in macaques is safe and does not disrupt immune development.
- Infant BCG vaccination induces transient antigen-specific immunity.
- Infant BCG vaccination may prime the immune system for enhanced responses upon later revaccination, indicative of trained innate immunity.
Abstract:
The BCG vaccine is given to millions of children globally but efficacy wanes over time and differences in the immune systems between infants and adults can influence vaccine efficacy. To this end, 34 rhesus macaques were vaccinated with BCG within seven days of birth and blood samples were collected over 88 weeks for quantification of blood cell populations. Overall, the composition of cell populations did not change significantly between BCG vaccinated and unvaccinated groups, and that BCG vaccination did not perturb normal development. In comparison to adult macaques, higher numbers of CD4+ T-cells, Tregs and NK cells were measured in the infant age group, suggesting a potential bias towards immunosuppressive and innate immune populations. Antigen-specific IFNγ secreting cell frequencies in infant BCG vaccinated animals were detectable in peripheral blood samples for 36 weeks after vaccination but declined following this. To evaluate the long-term impact of infant BCG vaccination on subsequent revaccination with BCG, a pilot study of three adult macaques received an aerosol BCG revaccination approximately 3 years after their initial BCG vaccination as infants. This induced an increase in PPD-specific IFNγ secreting cells, and increased secretion of the cytokines IFNγ and IL-1β, following stimulation with other microorganisms, which are signals associated with trained innate immunity.
Related Concept Videos
Vaccinations
Cells of the Adaptive Immune Response
Immunological Memory
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature...

