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

被引：8

作者：

McCracken, Michael K. ^{[1
]}

Kuklis, Caitlin H. ^{[1
]}

Kannadka, Chandrika B. ^{[1
]}

Barvir, David A. ^{[1
]}

Sanborn, Mark A. ^{[1
]}

Waickman, Adam T. ^{[1
]}

Siegfried, Hayden C. ^{[1
]}

Victor, Kaitlin A. ^{[1
]}

Hatch, Kristin L. ^{[1
]}

De la Barrera, Rafael ^{[2
]}

Walls, Shannon D. ^{[1
]}

Rutvisuttinunt, Wiriya ^{[1
]}

Currier, Jeffrey R. ^{[1
]}

Friberg, Heather ^{[1
]}

Jarman, Richard G. ^{[1
]}

Gromowski, Gregory D. ^{[1
]}

机构：

[1] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MA 20910 USA

[2] Walter Reed Army Inst Res, Pilot Bioprod Facil, Silver Spring, MA USA

来源：

NPJ VACCINES | 2021年 / 6卷 / 01期

关键词：

FLAVIVIRUS-NAIVE ADULTS; YELLOW-FEVER; HEALTHY-CHILDREN; IMMUNOGENICITY; SAFETY; CANDIDATE; INFECTION; IMMUNIZATION; PHASE-1; COMBINATIONS;

D O I：

10.1038/s41541-021-00339-y

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：12

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