FRLBC04 - Oral Abstract Session
BCG vaccination at birth induces non-specific CD4 T cell activation in HIV-exposed South African infants, which may increase HIV transmission through breastfeeding
Presented by Heather B. Jaspan (South Africa).
A.K. Hesseling1, J.-A.S. Passmore2, H. Gamieldien2, C.E. Jones3, W. Hanekom4, D.L. Sodora5, H.B. Jaspan2,5
1Stellenbosch University, Desmond Tutu TB Centre, Cape Town, South Africa, 2University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, Clinical Lab Sciences, Cape Town, South Africa, 3Imperial College London, Academic Department of Pediatrics, London, United Kingdom, 4University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, South African TB Vaccine Institute, Cape Town, South Africa, 5Seattle Biomedical Research Institute, Seattle, United States
Background: In sub-Saharan Africa, where BCG vaccine
is routinely given around birth to protect from disseminated TB, almost
a third of infants are HIV-exposed. HIV
preferentially infects activated CCR5+CD4+ cells. Highly HIV-exposed,
seronegative individuals have relatively decreased peripheral CD4 T cell
activation. We hypothesized that routine BCG vaccination of HIV-exposed neonates
causes non-specific CD4+ T cell activation.
Methods: HIV-exposed, uninfected
South African infants were randomized to receive either BCG at birth or at 8
weeks of age, and blood was collected at birth, 2 and 6 weeks. Unstimulated PBMCs were stained with viability dye, anti-CD3, -CD4, -CD8,
-CCR5, the activation markers CD38 and HLA-DR, and the proliferation marker
Ki67. PBMC and plasma cytokine mRNA and protein levels were measured using
RTPCR and Luminex respectively.
Results: At 6 weeks of age, there
was a significantly higher HLA-DR expression and CCR5, HLA-DR and CD38
co-expression on CD4+ T cells (p= .02 and p= .01 respectively; n=94)
in the infants who had received BCG at birth compared to unvaccinated infants
(delayed arm). In contrast, there
was no difference in CD8 T cell activation between BCG-vaccinated and
unvaccinated infants. The CCR5
agonist, MIP1β, was
significantly higher at 6 weeks in plasma of unvaccinated infants (p=.02). There
were no differences in plasma IFN-a, IFN-g, MCP-1, TNF-a, IL-8, GMCSF or IP-10 levels, nor differences in PBMC
IL-8, IL-10, TGF- β,
OAS or IP-10 mRNA levels, between vaccinated and unvaccinated infants.
Conclusions: BCG vaccination induces non-specific
CD4+ T cell activation and down-regulation of MIP-1β expression. This elevated T
cell activation may increase HIV infections in breastfed infants and may
contribute to rapid disease progression. Further research regarding the risks
and benefits of BCG vaccination in HIV-exposed infants is needed to inform
policy and practice.
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