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Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice |
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| Authors: | Smita Jaiswal Kenneth Smith Alejandro Ramirez Marcia Woda Pamela Pazoles Leonard D Shultz Dale L Greiner Michael A Brehm Anuja Mathew |
| Affiliation: | 1.Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, USA;2.Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA;3.The Jackson Laboratory, Bar Harbor Maine, Maine 04609, USA;4.Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA |
| Abstract: | 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 IL2rγnull 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. |
| Keywords: | B cells viral human transgenic mice dengue |