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

• Published in: Vaccine Vol. 29; no. 42; pp. 7267 - 7275
• Main Authors: Coller, Beth-Ann G, Clements, David E, Bett, Andrew J, Sagar, Sangeetha L, Ter Meulen, Jan H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 23-09-2011; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Cell culture; Cell Line; 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; Primates; Protein Conformation; Proteins; Recombinant; 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; Viruses; Vaccine; Subunit; Dengue; Recombinant
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2011.07.021

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.