Wloch, M. K. et al. Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects. J. Infect. Dis. 197, 1634-1642

Vical, Inc., San Diego, CA 92121, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 07/2008; 197(12):1634-42. DOI: 10.1086/588385
Source: PubMed

ABSTRACT 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.
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.
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.
The safety and immunogenicity data from this trial support further evaluation of VCL-CB01.

Download full-text


Available from: Mary K Wloch, Aug 19, 2015
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: The authors explore the sources of and solutions to robot contact instability associated with force feedback. The behavior of several linear robot models is analyzed in terms of the properties of their admittances. Using the novel technique of passive physical equivalents, an explanation for the often-observed instability of a force-controlled robot contacting a stiff surface is offered, and it is shown that a fundamental limit exists to the efficacy of any force feedback controller implemented on a robot with noncolocated actuators and sensors. Suggestions for improved force control involving both mechanical design and compensator design are also presented
    Robotics and Automation, 1989. Proceedings., 1989 IEEE International Conference on; 06/1989
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasmid DNA (pDNA) vaccines have generated significant interest for the prevention or treatment of infectious diseases. Broader applications may benefit from the identification of safe and potent vaccine adjuvants. This report describes the development of a novel polymer-based formulation to enhance the immunogenicity of pDNA-based vaccines. Plasmid DNA was formulated with a nonionic block copolymer, poloxamer CRL1005, and the cationic surfactant benzalkonium chloride (BAK) to produce a thermodynamically stable, self-assembling system. The influence of parameters such as polymer concentration and BAK composition on the immune responses was evaluated in mice vaccinated with pDNA encoding influenza nucleoprotein. At concentrations of 7.5 mg/ml CRL1005, 0.3 mM BAK and 5 mg/ml pDNA, CRL1005/BAK/pDNA particles had a mean diameter of 261 +/- 0.2 nm and a surface charge of - 11.6 +/- 0.9 mV. The negative surface charge and atomic force microscopy images suggested that pDNA binds to BAK adsorbed to the surface of poloxamer particles. The CRL1005/BAK/pDNA formulation significantly enhanced antigen-specific cellular and humoral immune responses, and increased transgene levels in muscle and serum. The complexity of the formulation was reduced by replacing the commercial BAK, which is a mixture of four alkyl chains, with a C14 BAK homolog. The substitution yielded an analytically preferable formulation with equivalent physical characteristics and immunogenicity. The results suggest that the CRL1005/BAK/pDNA formulation may enhance immunogenicity by improving the delivery of pDNA-based vaccines. This formulation is currently being evaluated for the prevention of CMV-associated disease in a phase 2 clinical trial.
    The Journal of Gene Medicine 07/2008; 10(7):770-82. DOI:10.1002/jgm.1199 · 2.47 Impact Factor
  • The Journal of Infectious Diseases 07/2008; 197(12):1631-3. DOI:10.1086/588386 · 5.78 Impact Factor
Show more