免疫初免恒河猴体内登革热疫苗病毒复制增强及中和抗体反应

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

作者信息

McCracken Michael K, Kuklis Caitlin H, Kannadka Chandrika B, Barvir David A, Sanborn Mark A, Waickman Adam T, Siegfried Hayden C, Victor Kaitlin A, Hatch Kristin L, De La Barrera Rafael, Walls Shannon D, Rutvisuttinunt Wiriya, Currier Jeffrey R, Friberg Heather, Jarman Richard G, Gromowski Gregory D

机构信息

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MA, USA.

Pilot Bioproduction Facility, Walter Reed Army Institute of Research, Silver Spring, MA, USA.

出版信息

NPJ Vaccines. 2021 May 21;6(1):77. doi: 10.1038/s41541-021-00339-y.

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.

抗体依赖增强作用（ADE）被怀疑会影响登革病毒（DENV）感染，但ADE在包含减毒活病毒成分的疫苗接种策略中所起的作用尚不清楚。我们在恒河猴中采用异源初免-加强策略，研究了用登革病毒纯化灭活疫苗（PIV）初免对四价减毒活疫苗（LAV）的影响。PIV初免后血清显示出低水平的中和抗体（NAb），但体外ADE活性为中度至高度。给予LAV后，PIV初免组的DENV-2 LAV峰值病毒血症比假初免组高1176倍，且峰值病毒血症与体外ADE相关。此外，PIV初免组在给予LAV后比假初免组有更平衡且更高的DENV-1-4 NAb血清转化和滴度。这些结果对开发有效的DENV疫苗初免-加强策略以及我们理解ADE在调节DENV复制中所起的作用具有启示意义。