2783. Expansion of Monocytic Myeloid-Derived Suppressor Cells in Infants with Severe Respiratory Syncytial Virus (RSV) Infection

BACKGROUND: RSV remains a leading cause for hospitalization of infants. The mechanisms associated with the ability of RSV to suppress the induction of an adequate immune response are not well understood and represent a challenge for vaccine development. Myeloid-derived-suppressor cells (MDSCs) have been shown to suppress CD8+ T cells in patients with malignancies. These immature myeloid cells are divided into three groups: granulocytic, monocytic, and undifferentiated. Of those, monocytic MDSCs (M-MDSCs) are considered to be key regulators of inflammatory responses during acute infections. Their potential role in the immunopathogenesis of RSV infection in infants is yet to be defined. METHODS: Single-center, prospective cohort study in previously healthy infants hospitalized with severe RSV lower respiratory tract infection (LRTI) and age-matched healthy controls (HC). Nasopharyngeal swabs for RSV detection and blood samples for cell immunophenotyping were analyzed at enrollment (D1), 1-month (D30), and 6-months (D180) follow-up visits. Disease severity was assessed using a clinical disease severity score (CDSS), duration of supplemental O2, and duration of hospitalization. RESULTS: We enrolled 39 infants with RSV LRTI (median [IQR] age: 3.3 [1.5–5.2] months) and 5 HC (5.9 [4.5–7.2] months). Infants with RSV infection demonstrated an expansion of M-MDSCs during the acute infection (D1) that resolved to numbers comparable to those in HC at follow-up visits (Figure 1A). In addition, numbers of CD8+ T cells were significantly reduced during the acute infection (D1) in RSV-infected infants, but also returned to the HC baseline on D30 and D180 (Figure 1B). Finally, the increase in M-MDSCs numbers and decrease in CD8+ T-cell numbers were associated with worse clinical outcomes as defined by duration of supplemental oxygen (>1 day), hospitalization (>48 hours), and clinical disease severity score (CDSS, > 9) (Figure 2). CONCLUSION: These findings suggest that an expansion of M-MDSCs may play a role in T-cell suppression in children with severe RSV disease. As new vaccines are being developed, it is critical to elucidate the immune suppressive mechanisms associated with RSV infection. [Image: see text] [Image: see text] DISCLOSURES: Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.