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: 6). 07/2008; 197(12):1634-42. DOI: 10.1086/588385
Source: PubMed


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.

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Available from: Mary K Wloch,
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    • "In consideration of the increasing number of patients who will receive an in vivo or in vitro T-cell depleted transplant, new strategies should be urgently adopted to prevent prolonged HCMV immunodeficiency and the emergence of severe HCMV-related complications. New antiviral drugs [18], vaccines [19,20], and reconstitution of HCMV cellular immunity [21-23] should be considered when designing new models of HCMV disease prevention. "
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    ABSTRACT: BackgroundHuman cytomegalovirus (HCMV) infection of the central nervous system (CNS) is a rare but life threatening condition which may follow hematopoietic stem cell transplantation. Diagnosis, monitoring and treatment approaches rely on anecdotal reports.Case presentationsThe different outcomes of HCMV CNS disease in an adult and a pediatric T-cell depleted hematopoietic stem cell transplant (HSCT) recipient are reported. In the first case, HCMV encephalitis emerged in the context of simultaneous impairment of the T- and B-cell immunity. Antiviral treatment only reduced viral load in peripheral blood and the patient died. In the second case, an HCMV radiculopathy was observed and antiviral treatment was adjusted on the basis of intrathecal drug level. In addition, donor HCMV-specific cytotoxic T lymphocytes (CTLs) were infused. Viral load in the CNS decreased and the patient recovered from the acute event. In neither case were drug-resistant HCMV variants observed in blood or CNS samples.ConclusionsT-cell depleted HSCT appears a predisposing condition for CNS HCMV infection since never observed in other HSCT recipients at our center in the last 15 years. Intensive diagnostic approaches and timely aggressive combination treatments might improve clinical outcome in these patients.
    BMC Infectious Diseases 10/2012; 12(1):238. DOI:10.1186/1471-2334-12-238 · 2.61 Impact Factor
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    • "In the guinea pig model gB DNA vaccination administered prior to conception offered some protection against congenital CMV transmission in the liveborn pups.111 A phase I study of a bivalent CMV DNA vaccine demonstrated safety and immunogenicity of the DNA vaccine.112 The effect of immune priming with a CMV DNA vaccine encoding pp65, IE1, and gB was tested by administering the Towne strain after vaccination and evaluating the immune response.113 "
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    International Journal of Women's Health 08/2010; 2(1):23-35.
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    • "A study by Wloch and colleagues at Vical Incorporated examined DNA immunizations of human volunteers with cytomegalovirus (CMV) plasmids formulated with a specific poloxamer adjuvant. In that study CMV-specific T-cell responses were detected in a majority of CMV sero-negative individuals who were vaccinated [29]. "
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    ABSTRACT: Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that "DNA vaccination" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens.
    Journal of Immune Based Therapies and Vaccines 10/2009; 7(1):3. DOI:10.1186/1476-8518-7-3
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