Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 240, Issue 1, Pages 67-78Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370214546273
Keywords
B cells; viral; human; transgenic mice; dengue
Categories
Funding
- pilot project [U19 AI57319]
- NIAID [U19 AI57234, R21AI103650]
- NIH [CA34196, 046629]
- NIH Diabetes Endocrinology Research Center (DERC) [DK52530]
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The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2r(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines.
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