Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques

• Main Authors: Michael K. McCracken, Caitlin H. Kuklis, Chandrika B. Kannadka, David A. Barvir, Mark A. Sanborn, Adam T. Waickman, Hayden C. Siegfried, Kaitlin A. Victor, Kristin L. Hatch, Rafael De La Barrera, Shannon D. Walls, Wiriya Rutvisuttinunt, Jeffrey R. Currier, Heather Friberg, Richard G. Jarman, Gregory D. Gromowski
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-05-01
• Series: npj Vaccines
• Online Access: https://doi.org/10.1038/s41541-021-00339-y

Abstract Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of priming with DENV purified inactivated vaccines (PIVs) on a tetravalent live attenuated vaccine (LAV). Sera exhibited low-level neutralizing antibodies (NAb) post PIV priming, yet moderate to high in vitro ADE activity. Following LAV administration, the PIV primed groups exhibited DENV-2 LAV peak viremias up to 1,176-fold higher than the mock primed group, and peak viremia correlated with in vitro ADE. Furthermore, PIV primed groups had more balanced and higher DENV-1–4 NAb seroconversion and titers than the mock primed group following LAV administration. These results have implications for the development of effective DENV vaccine prime-boost strategies and for our understanding of the role played by ADE in modulating DENV replication.