Myeloid‐derived suppressor cells and their association with vaccine immunogenicity in South African infants

The role of Myeloid‐Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety‐one South African infant‐mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette‐Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag‐specific CD4+ T cell proliferation and interferon gamma (IFN‐γ) production. Vaccine‐specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme‐Linked Immunosorbent assay (ELISA). MDSC frequency in mother‐infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN‐γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid‐Derived Suppressor Cells (PMN‐MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC‐mediated suppression of vaccine Ag‐specific IFN‐γ responses should be explored further, and considered when evaluating candidate infant vaccines. Graphical A longitudinal analysis of infant MDSC frequency and association with vaccine antigen recall responses. PMN‐MDSC present at infant vaccination reduces the probability of cellular IFN‐g release, but not proliferation or antibody production, upon subsequent ex‐vivo vaccine‐specific antigenic stimulation.