BCG vaccination causes immune activation of CD4 T-cells in infants

Heather Jaspan. © IAS/Deborah W. Campos - Commercialimage.net
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BCG vaccination, routinely given at birth to protect from tuberculosis (TB), causes an immune-activation of CD4 T cells, the HIV target cells, according to a South African study presented at the Nineteenth International AIDS Conference in Washington DC.

This immune activation may increase the risk of infant HIV infection through breastfeeding, particularly in cases where the infant is not receiving antiretroviral prophylaxis or where the mother is not taking fully suppressive antiretroviral therapy.

The BCG vaccine is given routinely to infants in settings where TB is endemic and is recommended for HIV-positive children in South African treatment guidelines. The BCG vaccine has been shown to be a safe and effective vaccination against disseminated TB in children without HIV. Although it is associated with a 1% risk of disseminated disease in HIV-positive children, it is still recommended to be administered to all infants at birth since their HIV status is often only definitively known once they are 4 to 6 weeks old.

Glossary

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

bacteria

Single-celled micro-organisms.

target cell

Type of cell that HIV or another virus or bacteria infects.

replication competent

The reservoir contains both replication-competent HIV, which has all necessary components to be able to replicate once emerging from the latent stage, and replication-defective HIV.

The study randomised 118 HIV-exposed, uninfected infants from Khayelitsha, a large township outside of Cape Town, where the antenatal HIV-prevalence is 30%. 62 infants were given the BCG vaccination at birth as per recommended guidelines, while 56 infants were given their BCG vaccinations at the age of 8 weeks. Blood was collected at birth, 2 weeks, 6 weeks, and 8 weeks for analysis.

The results at 6 weeks showed significantly higher HLA-DR expression on CD4 T cells among the infants who had received BCG at birth, compared with those in the delayed group (p=0.024). The expression of HLA-DR on regulatory T cells correlates positively with immune activation in HIV. In addition, the results at 6 weeks showed significantly higher CCR5, HLA-DR and CD38 co-expression on CD4 T cells in infants who received BCG at birth compared with those in the delayed group (p=0.01). The CCR5 agonist, MIP-1-beta, was significantly higher at 6 weeks in the plasma of unvaccinated infants (p =0.02).

There was no difference in the activation of CD8 T cell activation between activation between BCG-vaccinated and unvaccinated infants.

The immune activation of CD4 T cells places breastfed infants especially at an increased risk of HIV infection and disease progression. 39% of mother-to-child HIV transmission is caused by breastfeeding from HIV-infected mothers. However, formula feeding is associated with morbidity and mortality in sub-Saharan Africa and breastfeeding is therefore recommended.

There was no significant difference between the groups in the median maternal CD4 count, the mean infant birth weight, infant gender or whether or not the infants were breastfed or formula fed.

Although other vaccinations given at 6 weeks are associated with increase in activation, the immune activation effect of BCG is sustained at 8 weeks.

“We think these data have important implications both for the timing of infant BCG vaccination in HIV-exposed infants and for perhaps the use of live replication competent bacteria as HIV and other vaccine vectors in these infants,” said Dr Heather Jaspan, one of the authors of the study.  

Further research regarding the risks and benefits of BCG vaccination in HIV-exposed infants is needed to inform policy and practice.

References

Jaspan H et al. BCG Vaccination at Birth Induces Non-Specific CD4 T-Cell Activation in HIV-Exposed South African Infants. 19th International Conference on AIDS, abstract FRLBC04, Washington, DC, July 2012.

View the abstract on the conference website.

View webcast of the conference session.