Detection and pharmacokinetics of a cytomegalovirus (<scp>CMV</scp>) <scp>DNA</scp> plasmid in human plasma during a clinical trial of an intramuscular <scp>CMV</scp> vaccine in hematopoietic stem cell transplant recipients

Salimnia, Hossein; Fairfax, Marilynn R.; Chandrasekar, P.H.

doi:10.1111/tid.12315

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…ASP0113 plasmid concentrations in plasma rapidly declined and were undetectable by PCR within 1 week of dosing, consistent with previous results 25 . The dual plasmid concentration peaks observed in the 48 hours after dosing likely reflect initial venous absorption into plasma and slower lymphatic absorption from the injection site.…”

Section: Discussionsupporting

confidence: 89%

Pharmacokinetics and Immunogenicity of ASP0113 in CMV‐Seronegative Dialysis Patients and CMV‐Seronegative and ‐Seropositive Healthy Subjects

Bonate

Sant

Cho

et al. 2020

Clinical Pharm in Drug Dev

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Cytomegalovirus (CMV) infection causes significant morbidity and mortality in immunocompromised transplant patients. ASP0113, a first-in-class DNA vaccine containing plasmids encoding CMV phosphoprotein 65 and glycoprotein B (gB), was evaluated in a phase 1b, subject-blinded study in CMV-seropositive (n = 13) and CMV-seronegative (n = 12) healthy and CMV-seronegative dialysis subjects (n = 12) randomized to ASP0113 or placebo. End points included pharmacokinetics, anti-gB antibody levels, phosphoprotein 65-specific T-cell responses measured by ex vivo enzyme-linked immune absorbent spot (ELISpot) assay and 10-day cultured ELISpot and Stat T-cell activation assays, and safety. ASP0113 concentrations peaked at 2-10 and 24-48 hours; the pharmacokinetics were similar across groups. No group demonstrated significant anti-gB antibody responses. T-cell responder rates in the cultured ELISpot assay were 8/12 (66.7%, 95%CI 35% to 90%) and 4/12 (33.3%, 95%CI 10% to 65%) in CMV-seronegative healthy subjects and dialysis patients, respectively, whereas ex vivo ELISpot assay response rates were 4/11 (36.4%, 95%CI 11% to 69%) and 0/12, respectively. Responses peaked at week 27, with lower magnitude observed in CMV-seronegative dialysis patients versus CMV-seronegative healthy subjects. No serious adverse events occurred; the most common adverse event in ASP0113-vaccinated patients was injection-site pain (64.9%). Some CMV-seronegative healthy subjects and dialysis patients had T-cell responses; no humoral responses were detected.

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Section: Discussionsupporting

confidence: 89%

Pharmacokinetics and Immunogenicity of ASP0113 in CMV‐Seronegative Dialysis Patients and CMV‐Seronegative and ‐Seropositive Healthy Subjects

Bonate

Sant

Cho

et al. 2020

Clinical Pharm in Drug Dev

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“…Additional study is needed to determine its utility and the test sensitivity is low in patients with lymphopenia, but the assay has been able to predict disease and may help with stratifying patient risks for CMV and guiding prophylaxis or preemptive treatment. 73,80,142,144 Finally, while none is available for clinical use, CMV vaccines are in development, with some in phase II clinical trials [145][146][147][148] and an ongoing phase III DNA vaccine trial. 149…”

Section: Prognosis and Therapymentioning

confidence: 99%

Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

Reid

Lynch

Weigt

et al. 2016

Semin Respir Crit Care Med

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Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein-Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies.

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Detection and pharmacokinetics of a cytomegalovirus (CMV) DNA plasmid in human plasma during a clinical trial of an intramuscular CMV vaccine in hematopoietic stem cell transplant recipients

Cited by 2 publications

References 11 publications

Pharmacokinetics and Immunogenicity of ASP0113 in CMV‐Seronegative Dialysis Patients and CMV‐Seronegative and ‐Seropositive Healthy Subjects

Pharmacokinetics and Immunogenicity of ASP0113 in CMV‐Seronegative Dialysis Patients and CMV‐Seronegative and ‐Seropositive Healthy Subjects

Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

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