Journal
VACCINE
Volume 29, Issue 42, Pages 7267-7275Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.07.021
Keywords
Dengue; Vaccine; Recombinant; Subunit
Categories
Funding
- NIAID NIH HHS [U01 AI056410-03, UC1 AI062481-01, R44 AI035401-02A1] Funding Source: Medline
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Challenges associated with the interference observed between the dengue virus components within early tetravalent live-attenuated vaccines led many groups to explore the development of recombinant subunit based vaccines. Initial efforts in the field were hampered by low yields and/or improper folding, but the use of the Drosophila S2 cell expression system provided a mechanism to overcome these limitations. The truncated dengue envelope proteins (DEN-80E) for all four dengue virus types are expressed in the S2 system at high levels and have been shown to maintain native-like conformation. The DEN-80E proteins are potent immunogens when formulated with a variety of adjuvants, inducing high titer virus neutralizing antibody responses and demonstrating protection in both mouse and non-human primate models. Tetravalent vaccine formulations have shown no evidence of immune interference between the four DEN-80E antigens in preclinical models. Based on the promising preclinical data, the recombinant DEN-80E proteins have now advanced into clinical studies. An overview of the relevant preclinical data for these recombinant proteins is presented in this review. (C) 2011 Elsevier Ltd. All rights reserved.
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