# Immune cell population dynamics following neonatal BCG vaccination and aerosol BCG revaccination in rhesus macaques

## TL;DR

This study examines how BCG vaccination in infant rhesus macaques affects immune cell populations and responses over time, including the impact of later revaccination.

## Contribution

The study provides insights into immune dynamics following neonatal BCG vaccination and its long-term effects on revaccination responses in non-human primates.

## Key findings

- BCG vaccination in infants did not significantly alter blood cell population composition compared to unvaccinated controls.
- Infant BCG-vaccinated macaques showed detectable antigen-specific IFNγ secreting cells for 36 weeks, which then declined.
- Aerosol BCG revaccination in adults previously vaccinated as infants increased PPD-specific IFNγ and cytokine secretion, suggesting 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.