Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections.
Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections.
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DOI：
10.4049/jimmunol.1700029
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发表时间：
2017-05-15
期刊：
影响因子：
--
通讯作者：
Harris E
中科院分区：
文献类型：
--
作者：
Hertz T;Beatty PR;MacMillen Z;Killingbeck SS;Wang C;Harris E
Dengue is a global public health problem and is caused by four dengue virus serotypes (DENV1-4). A major challenge in dengue vaccine development is that cross-reactive anti-DENV antibodies can be protective or potentially enhance disease via antibody-dependent enhancement (ADE). DENV nonstructural protein 1 (NS1) has long been considered a vaccine candidate as it avoids ADE. Here, we evaluated survival to challenge in a lethal DENV vascular leak model in mice immunized with NS1 combined with alum, Monophosphoryl Lipid A + AddaVax (MA), or Sigma Adjuvant System + CpG DNA, compared to mice infected with a non-lethal dose of DENV2 and mice immunized with ovalbumin (negative control). We characterized antibody responses to DENV-1, -2 and -3 NS1 using an antigen microarray tiled with 20-mer peptides overlapping by 15 amino acids and identified 5 regions of DENV NS1 with significant levels of antibody reactivity in the NS1+MA group. Additionally, we profiled the antibody responses to NS1 of humans naturally infected with DENV2 or DENV3 in serum samples from Nicaragua collected at acute, convalescent and 12-month timepoints. One region in the “wing” domain of NS1 was immunodominant in both mouse vaccination and human infection studies, and two regions were identified only in NS1-immunized mice; thus, vaccination can generate antibodies to regions that are not targeted in natural infection and could provide additional protection against lethal DENV infection. Overall, we identified a small number of immunodominant regions, which were in functionally important locations on the DENV NS1 protein and are potential correlates of protection.
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影响因子：
17.1
作者：
Beatty, P. Robert;Puerta-Guardo, Henry;Harris, Eva
通讯作者：
Harris, Eva
影响因子：
2.7
作者：
BLOK, J;GIBBS, AJ;VITARANA, UT
通讯作者：
VITARANA, UT
DOI：
10.4269/ajtmh.1989.41.576
发表时间：
1989-11-01
影响因子：
3.3
作者：
KAUFMAN, BM;SUMMERS, PL;ECKELS, KH
通讯作者：
ECKELS, KH
影响因子：
7
作者：
Alving CR;Peachman KK;Rao M;Reed SG
通讯作者：
Reed SG
影响因子：
4.6
作者：
Foged, Camilla;Hansen, Jon;Agger, Else Marie
通讯作者：
Agger, Else Marie