487. Analysis of the Association between Specific Antibody Response against Respiratory Syncytial Virus Fusion Protein Conformations and Life-Threatening Infection in Previously Healthy Infants

Abstract

Abstract Background Specific humoral response against pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a role against severe infection. We aimed to analyze the association between serum IgG titers against pre-F and post-fusion (post-F) conformations of RSV F protein and life-threatening RSV disease (LTD) in previously healthy infants. Methods Prospective cohort study including previously healthy infants < 12 months, hospitalized with a first RSV infection, in 2017-2019. Patients were defined to have LTD when required intensive care and ventilatory support. Pre-F exclusive and post-F-specific antibody responses were determined by post-F competition and non-competitive immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. Viral load (VL) was assessed by qRT-PCR from nasopharyngeal aspirates collected on admission. Serum samples were collected within 72 h from admission and in convalescence (between 14 to 60 days). Results Seventy-five patients were included, median age 3 months, 60% (n=45) were males; 21 patients developed LTD. Importantly, acute and convalescent post-F and pre-F exclusive IgG titers did not associate with LTD (Fig 1). There was a positive correlation between neutralizing antibody titers and pre-F exclusive IgG titers (p=0.016). Post-F and pre-F exclusive IgG titers negatively correlated with age in acute phase (p< 0.0001 and p= 0.0009). In acute phase, post-F and pre-F exclusive IgG titers were higher in patients ≤ 2 months (Fig 2). Patients > 2 months increased post-F and pre-F exclusive IgG titers in convalescence. Additionally, post-F and pre-F exclusive titers did not correlate with VL, and VL was not related to LTD. Conclusion -Pre-F exclusive and post-F IgG titers did not associate with LTD, even though pre-F exclusive IgG correlated with neutralizing antibody titers. -Infants under two months of age developed a lower humoral response, likely due to an interference by maternal antibodies and/or immunological immaturity. -These findings highlight the importance of fully characterizing the immune response against RSV and its association with disease severity for the development of preventive strategies. Disclosures Barney S. Graham, MD, PhD, BSG: BSG is an inventor on patents for the stabilization of the RSV F protein (WO2014160463A1, Prefusion RSV F proteins and their use).|National Institutes of Health: Inventor on patents for RSV vaccines|National Institutes of Health: inventor on patents for measles and other paramyxovirus vaccines.