Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial

• Published in: Vaccine Vol. 29; no. 5; pp. 960 - 968
• Main Authors: Beckett, Charmagne G., Tjaden, Jeffrey, Burgess, Timothy, Danko, Janine R., Tamminga, Cindy, Simmons, Monika, Wu, Shuenn-Jue, Sun, Peifang, Kochel, Tadeusz, Raviprakash, Kanakatte, Hayes, Curtis G., Porter, Kevin R.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 29.01.2011; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; adults; Allergy and Immunology; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Clinical trials; Dengue; Dengue - prevention & control; Dengue fever; Dengue Vaccines - administration & dosage; Dengue Vaccines - adverse effects; Dengue Vaccines - immunology; Dengue virus; Deoxyribonucleic acid; DNA; DNA vaccines; Enzymes; Fundamental and applied biological sciences. Psychology; genes; Health care; Human subjects; Humans; immune response; Immunization, Secondary - methods; Immunogenicity; Injections, Intramuscular; interferon-gamma; Microbiology; Middle Aged; muscles; neutralizing antibodies; Pain; Pain - chemically induced; plasmid vectors; recombinant vaccines; Safety; serotypes; Skin Diseases - chemically induced; T-lymphocytes; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - immunology; Vector-borne diseases; Young Adult; Clinical trials; Dengue; DNA vaccines; Infection; Viral disease; Arbovirus disease; Dengue 1; Clinical trial; Genetic vaccine
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2010.11.050

Candidate dengue DNA vaccine constructs for each dengue serotype were developed by incorporating pre-membrane and envelope genes into a plasmid vector. A Phase 1 clinical trial was performed using the dengue virus serotype-1 (DENV-1) vaccine construct (D1ME100). The study was an open-label, dose-escalation, safety and immunogenicity trial involving 22 healthy flavivirus-naïve adults assigned to one of two groups. Each group received three intramuscular injections (0, 1, and 5 months) of either a high dose (5.0mg, n=12) or a low dose (1.0mg, n=10) DNA vaccine using the needle-free Biojector® 2000. The most commonly reported solicited signs and symptoms were local mild pain or tenderness (10/22, 45%), local mild swelling (6/22, 27%), muscle pain (6/22, 27%) and fatigue (6/22, 27%). Five subjects (41.6%) in the high dose group and none in the low dose group developed detectable anti-dengue neutralizing antibodies. T-cell IFN gamma responses were detected in 50% (4/8) and 83.3% (10/12) of subjects in the low and high dose groups, respectively. The safety profile of the DENV-1 DNA vaccine is acceptable at both doses administered in the study. These results demonstrate a favorable reactogenicity and safety profile of the first in human evaluation of a DENV-1 DNA vaccine.