The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease

Abstract 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 improp...

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Veröffentlicht in:Vaccine 2011-09, Vol.29 (42), p.7267-7275
Hauptverfasser: Coller, Beth-Ann G, Clements, David E, Bett, Andrew J, Sagar, Sangeetha L, Ter Meulen, Jan H
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container_end_page 7275
container_issue 42
container_start_page 7267
container_title Vaccine
container_volume 29
creator Coller, Beth-Ann G
Clements, David E
Bett, Andrew J
Sagar, Sangeetha L
Ter Meulen, Jan H
description Abstract 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.
doi_str_mv 10.1016/j.vaccine.2011.07.021
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subjects adjuvants
Adjuvants, Immunologic - administration & dosage
Allergy and Immunology
Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
antigens
Cell culture
Cell Line
clinical trials
Dengue
Dengue - prevention & control
Dengue fever
Dengue Vaccines - administration & dosage
Dengue Vaccines - genetics
Dengue Vaccines - immunology
Dengue virus
Dengue Virus - genetics
Dengue Virus - immunology
Drosophila
E coli
Gene Expression
Humans
Hypotheses
Infections
Mice
neutralization
neutralizing antibodies
Primates
Protein Conformation
Proteins
Recombinant
recombinant proteins
Subunit
Vaccine
Vaccines
Vaccines, Subunit - administration & dosage
Vaccines, Subunit - genetics
Vaccines, Subunit - immunology
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - genetics
Vaccines, Synthetic - immunology
Vector-borne diseases
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
viral load
Viruses
title The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease
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