Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial.
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 (D1ME(100)). 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.
Naval Medical Research Center, Viral & Rickettsial Diseases Department, Infectious Diseases Directorate, Silver Spring, MD, USA. charmagne.beckett@med.navy.mil
Charmagne G
CG
Beckett
Jeffrey
J
Tjaden
Timothy
T
Burgess
Janine R
JR
Danko
Cindy
C
Tamminga
Monika
M
Simmons
Shuenn-Jue
SJ
Wu
Peifang
P
Sun
Tadeusz
T
Kochel
Kanakatte
K
Raviprakash
Curtis G
CG
Hayes
Kevin R
KR
Porter
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007273:Injections, Intramuscular; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D012871:Skin Diseases / Q000139:chemically induced; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D019444:Vaccines, DNA