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

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 (+4 others)
2021 npj Vaccines  
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
more » ... E 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.
doi:10.1038/s41541-021-00339-y pmid:34021159 fatcat:fqrfkbxlizevbkn76tupi4ofze