Dynamics of antibody responses following primary dengue virus 3 infections in Nicaragua reveals differential waning of IgG responses by antigen and subclass 3546

Abstract Description The 4 dengue virus serotypes (DENV1–4) are mosquito-borne flaviviruses of major global importance. Although a primary (1°) DENV infection has been thought to induce antibodies (Abs) that wane over 2 years to titers that can enhance disease severity in secondary DENV infections, we previously showed that Inhibition ELISA (iELISA) titers following 1° DENV remain stable up to 11 years. However, iELISA cannot differentiate between IgG subclass or specific DENV antigens, which may wane at different rates. Here, we investigate Ab dynamics following 1° DENV3 infections using a 15-plex Luminex assay measuring total IgG and IgG subclasses against envelope (E), E domain III (EDIII), and NS1 of DENV1-4 and the related Zika virus up to 42 months post-infection (mpi) in 60 children from the long-standing Pediatric Dengue Cohort Study in Managua, Nicaragua. IgG targeting whole E remained stable through 42 mpi while anti-EDIII IgG levels showed slight decline (p < 0.01), suggesting different waning rates across the E protein. The most significant drop was in anti-NS1 IgG, with a steep decline between 6 and 18 mpi (p < 0.0001). Anti-NS1 IgG3 was still detectable in 41% of samples at 42 mpi, contrary to reports of IgG3 serving as a marker of recent infection. Ongoing work focuses on Abs to NS1 domains and epitopes associated with protection and E epitopes associated with enhancement. These findings modify our understanding of DENV Ab dynamics with implications for natural infections and vaccines. Funding Sources P01AI106695, U01AI153416 Topic Categories Viral Immunology (VIR)