Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects.
BACKGROUND
VCL-CB01, a candidate cytomegalovirus (CMV) DNA vaccine that contains plasmids encoding CMV phosphoprotein 65 (pp65) and glycoprotein B (gB) to induce cellular and humoral immune responses and that is formulated with poloxamer CRL1005 and benzalkonium chloride to enhance immune responses, was evaluated in a phase 1 clinical trial.


METHODS
VCL-CB01 was evaluated in 44 healthy adult subjects (22 CMV seronegative and 22 CMV seropositive) 18-43 years old. Thirty-two subjects received 1- or 5-mg doses of vaccine on a 0-, 2-, and 8-week schedule, and 12 subjects received 5-mg doses of vaccine on a 0-, 3-, 7-, and 28-day schedule.


RESULTS
Overall, the vaccine was well tolerated, with no serious adverse events. Local reactions included mild to moderate injection site pain and tenderness, induration, and erythema. Systemic reactions included mild to moderate malaise and myalgia. All reactions resolved without sequelae. Through week 16 of the study, immunogenicity, as measured by enzyme-linked immunosorbant assay and/or ex vivo interferon (IFN)-gamma enzyme-linked immunospot assay, was documented in 45.5% of CMV-seronegative subjects and in 25.0% of CMV-seropositive subjects who received the full vaccine series, and 68.1% of CMV-seronegative subjects had memory IFN-gamma T cell responses at week 32.


CONCLUSIONS
The safety and immunogenicity data from this trial support further evaluation of VCL-CB01.
Wloch
Mary K
MK
Vical, Inc., San Diego, CA 92121, USA. mwloch@vical.com
Smith
Larry R
LR
Boutsaboualoy
Souphaphone
S
Reyes
Luane
L
Han
Christina
C
Kehler
Jackie
J
Smith
Heather D
HD
Selk
Linda
L
Nakamura
Ryotaro
R
Brown
Janice M
JM
Marbury
Thomas
T
Wald
Anna
A
Rolland
Alain
A
Kaslow
David
D
Evans
Thomas
T
Boeckh
Michael
M
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D003587:Cytomegalovirus / Q000276:immunology; D022482:Cytomegalovirus Vaccines / Q000009:adverse effects* / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007700:Kinetics; D008297:Male; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D019444:Vaccines, DNA / Q000009:adverse effects* / Q000276:immunology*
D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D019444:Vaccines, DNA