Abstract
Abstract Active tuberculosis infection is the leading cause of death for people living with HIV. HIV+ infants in resource poor settings are exposed to tuberculosis and the vaccine M. bovis BCG, which can become disseminated in immune-compromised hosts. How BCG impacts the HIV infected immune system is poorly understood. Here, we used the SIV-macaque model to evaluate BCG vaccination in infant Rhesus macaques infected with SIV (N=7) or uninfected controls (N=5). Blood was obtained from macaques (0–10 months of age) that were either SIV-infected or uninfected, and assessed at multiple timepoints following intradermal vaccination with BCG (Danish strain). The frequency of CCR5+ CD4+ T cells significantly increased following BCG, with a greater difference observed in SIV+ (33.9 fold change compared to pre-BCG vaccination) compared to uninfected (2.7 fold) infants. Markers of activation were assessed within the B cells (CD20), monocytes (CD14), mDCs (CD11c), and pDCs (CD123). We observed an increase in the costimulatory molecule CD86 in both SIV-infected and uninfected macaques following BCG vaccination, with higher overall levels observed SIV+ infants. These elevated levels of CD86+ cells were observed for both B cells (1.4% uninfected and 4% in SIV+) and mDCs (4.1% uninfected and 16.1% SIV+) after BCG vaccination, which is in part a reflection of higher baseline immune activation in the SIV+ infants. These studies identify changes associated with BCG vaccination in SIV+ infant macaques, which include an increase in potential SIV target cells (CCR5+/CD4+) and elevated activation of B cells and mDCs in the blood. Studies are now underway to evaluate these findings in tissues from these infants.
Published Version
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