79. Mucosal Interferon (IFN) Responses in Infants with Respiratory Syncytial Virus (RSV) Infection to Inform Live Attenuated Vaccine (LAV) Development

Abstract

BackgroundRespiratory syncytial virus (RSV) is a leading cause of hospitalization for infants. Several vaccine strategies for RSV are being developed. Among those, live attenuated vaccine (LAV) represent an attractive alternative for young children as they mimic natural infection and induce protective immunity without causing enhanced disease. However, markers of reactogenicity and/or innate immune protection in the respiratory mucosa are not well defined. The objective of this study was to assess mucosal markers, including innate immune cytokine profiles and RSV loads (VL), and their potential association with protection from severe disease in infants with natural RSV infection.MethodsSingle-center, prospective study in previously healthy infants with mild (outpatients; OP) and severe (inpatients; IP) RSV infection, and aged-matched healthy controls (HC). Nasopharyngeal (NP) swabs were obtained at enrollment in all subjects to measure VL by PCR, and cytokine concentrations (conc.) using a 13-plex panel that included: Type-I, type-II, and type-III IFN, and inflammatory cytokines. Cytokine conc. and VL were compared according to hospitalization status (OP vs. IP).ResultsFrom 2014 to 2017 we enrolled 105 infants: 48 with severe RSV infection (IP; median IQR age: 2.3 [1.1–5.5] months), 36 with mild disease (OP; 6.4 [3.8–9.3] months), and 20 HC (4.9 [2.8–7.2] months). The median duration of symptoms at enrollment was 4 days for both IP and OP. IL-1β, TNF-α, and IL-10 were detected more frequently in RSV infants than in HC (39% vs. 5%, respectively), but median conc. in IP and OP were not different (P > 0.05). Detection and/or conc. of IFN-β, IP-10, IFN-γ and type III IFN (IFN-λ1, IFN-λ2/3) were significantly greater in OP vs. IP, who also had higher VL (Table 1). In addition, IP-10 (r = 0.6; P < 0.001) and IFN-λ conc. (r = 0.55, P < 0.0001) significantly correlated with RSV VL.ConclusionInfants with mild RSV infection had higher VL and a more robust type-I, -II, and -III IFN responses than those hospitalized with severe disease. These findings suggest that increase conc. of mucosal IFNs are associated with protection against severe RSV infection, and could potentially be used as surrogate markers to help the development of LAV for RSV infection in young children. DisclosuresOctavio 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.