Fellowship completed

May 5, 2022

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IMPRINT fellow Alansana Darboe from the Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine completed his project ‘Understanding interactions between Maternal IgG and Neonatal Innate Immune Cells (MINIC).’ 

It is still not well understood whether vaccines given to women in pregnancy (maternal immunisation) influence the developing immune system of the newborn baby. However, this knowledge is important to make sure that current and future vaccines used in pregnancy can be optimised in the most efficient and protective way. Whilst we have better insights into the effect of the maternal vaccines on the antigen-specific, acquired (T and B cells) immune responses in the newborn, there remains a gap in knowledge about the effects of maternal vaccination on infant natural defense cells (innate immunity).    

To investigate this, IMPRINT fellow Alansana Darboe and his team developed a prototype laboratory assay that allows the examination of the effects of maternal antibodies on the natural defense cells using newborn cord blood, specifically looking at monocytes and natural killer (NK) cells. The researchers used the tetanus vaccine as their candidate maternal vaccination model, given that this vaccine is routinely given to pregnant women in The Gambia.      

They found that innate cells called monocytes were significantly activated following exposure of these cells to tetanus vaccine antigens in the presence of 40% cord maternal antibody plasma. But this effect was not observed using 10% and 20% plasma antibody concentrations and in the presence of purified tetanus protein. Specifically, Darboe and his team saw that these monocyte subsets could be modified in their prototype assay, and they could change their ability to produce cytokines, namely, TNF-a, IL-6, and co-stimulatory molecule CD40. Cytokines and co-stimulatory receptors are small molecules important in cell-to-cell communication in order to produce an effective natural immune response. In contrast, changes in NK cell functionality could not be seen using the team’s laboratory settings.    

The main outcome of the study is that Darboe and his co-investigators could identify for the first time to their knowledge the induction and activation of innate cells (monocyte subsets) in maternal vaccination using cord blood, but this modification was not seen in the case of NK cells using their experimental settings.     

This prototype assay could serve to evaluate the potential impact of other maternal vaccines on neonatal innate cellular responses in early life. This knowledge will help us to understand if there is potential for such observed changes to have a clinical impact on longer-term antigen-specific immunity in infants or not.    

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