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Sequential immunization induces strong and broad immunity against all four dengue virus serotypes.
Name
s41541-020-00216-0.pdf
Description
Published version
Size
1.63 MB
Format
Adobe PDF
Checksum (MD5)
e887a4eb3f2d324fab558b4e53c461ac
Author(s)
Hou, Jue
Shrivastava, Shubham
Loo, Hooi Linn
Wong, Lan Hiong
Ooi, Eng Eong
Chen, Jianzhu
Date Issued
July 24, 2020
Journal
NPJ Vaccines
Version
Final published version
Abstract
A major challenge in dengue vaccine development is the need to induce immunity against four dengue (DENV) serotypes. Dengvaxia®, the only licensed dengue vaccine, consists of four variant dengue antigens, one for each serotype. Three doses of immunization with the tetravalent vaccine induced only suboptimal protection against DENV1 and DENV2. Furthermore, vaccination paradoxically and adversely primes dengue naïve subjects to more severe dengue. Here, we have tested whether sequential immunization induces stronger and broader immunity against four DENV serotypes than tetravalent-formulated immunization. Mice were immunized with four DNA plasmids, each encoding the pre-membrane and envelope from one DENV serotype, either sequentially or simultaneously. The sequential immunization induced significantly higher levels of interferon (IFN)γ- or tumor necrosis factor (TNF)α-expressing CD4+ and CD8+ T cells to both serotype-specific and conserved epitopes than tetravalent immunization. Moreover, sequential immunization induced higher levels of neutralizing antibodies to all four DENV serotypes than tetravalent vaccination. Consistently, sequential immunization resulted in more diversified immunoglobulin repertoire, including increased complementarity determining region 3 (CDR3) length and more robust germinal center reactions. These results show that sequential immunization offers a simple approach to potentially overcome the current challenges encountered with tetravalent-formulated dengue vaccines.
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1038/s41541-020-00216-0
