Immune cell population dynamics following neonatal BCG vaccination and aerosol BCG revaccination in rhesus macaques.
Laura Sibley, Charlotte Sarfas, Alexandra L Morrison, Jessica Williams, Konstantinos Gkolfinos, Adam Mabbutt, William Eckworth, Steve Lawrence, Mike Dennis, Andrew White, Sally Sharpe
Author Information
Laura Sibley: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Charlotte Sarfas: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Alexandra L Morrison: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Jessica Williams: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Konstantinos Gkolfinos: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Adam Mabbutt: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
William Eckworth: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Steve Lawrence: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Mike Dennis: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
Andrew White: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK. Andrew.White@UKHSA.gov.uk.
Sally Sharpe: UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
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 IFN�� 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 IFN�� secreting cells, and increased secretion of the cytokines IFN�� and IL-1��, following stimulation with other microorganisms, which are signals associated with trained innate immunity.