Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects.

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.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission.
    Virology 07/2014; s 460–461:55–65. DOI:10.1016/j.virol.2014.04.032 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that causes significant disease worldwide. Although evidence exists that neutralizing antibodies and cytotoxic T cell responses to HCMV antigens can prevent HCMV disease and/or infection, there are no approved vaccines to prevent HCMV disease. Over the past 10 years, multiple HCMV vaccines have been tested in man but only partial protection has been achieved in these studies. HCMV contains multiple surface-expressed glycoproteins that are critical to viral entry, including gB, the gM/gN complex, the gH/gL complex, and a pentameric gH/gL/UL128/UL130/UL131A complex. Recently we showed that viral replicon particles (VRPs) expressing the gH/gL complex elicited more potently neutralizing antibodies than VRPs expressing gB in mice. Here we compare the immunogenicity of VRPs encoding the HCMV gH/gL and pentameric complexes, as well as purified gH/gL and pentameric complexes administered in the presence or absence of the MF59 adjuvant. The results of these studies indicate that the pentameric complex elicits significantly higher levels of neutralizing antibodies than the gH/gL complex, and that MF59 significantly increases the potency of each complex. In addition, we show that animals immunized with pentamer encoding VRPs or the pentameric subunit produce antibodies that recognize a broad range of antigenic sties on the complex. Taken together, these studies support the utility of the pentameric complex in HCMV vaccine candidates.
    Vaccine 05/2014; DOI:10.1016/j.vaccine.2014.05.004 · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose of review Despite significant improvements in the management of patients undergoing allogeneic stem cell transplantation, including anticytomegalovirus (CMV) prophylaxis and treatment, clinical handling of CMV infection remains challenging in the light of high morbidity and mortality rates. Thus, novel strategies and agents to control CMV infection and disease will be discussed. Recent findings Novel assays to quantify viral load and detect antiviral resistance mechanisms on the basis of next-generation sequencing have been described and will help to earlier and more effectively control CMV infection. In addition, safer and more effective antiviral agents are now available and strategies to boost the CMV-directed immune responses are being explored in the clinic. Summary Novel diagnostic tests, novel agents and the increased understanding of the immune response to CMV have and will have a major impact on improving the management of CMV infection in hematological patients.
    Current Opinion in Hematology 11/2014; 21(6):470-475. DOI:10.1097/MOH.0000000000000090 · 4.05 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014