Delving into the Latest Updates on Cytomegalovirus peptide vaccine(City of Hope National Medical Center) with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide vaccine, Prophylactic vaccine

Synonyms

CMV fusion peptide vaccines, CMVPepVax, CMVpp65-A*0201 peptide vaccine

+ [1]

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [3]

Active Indication

Adult Acute Lymphocytic LeukemiaAdult Acute Myeloblastic LeukemiaAdult Lymphoblastic Lymphoma+ [9]

Inactive Indication

Precancerous Conditions

Originator Organization

City of Hope National Medical Center

Active Organization

National Cancer Institute

City of Hope National Medical Center

Inactive Organization

University of Minnesota

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 1120173650

This randomized phase II trial studies how well vaccine therapy works in reducing the frequency of cytomegalovirus severe infections (events) in patients with hematologic malignancies undergoing donor stem cell transplant. Vaccines made from a peptide may help the body build an effective immune response and may reduce cytomegalovirus events after donor stem cell transplant.

Start Date21 May 2015

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

NCT00712634

/ CompletedPhase 1IIT

A Phase I Dose Escalation Study of Lipopeptide Vaccines With Activity Against Human Cytomegalovirus

RATIONALE: Vaccines may help the body build an effective immune response against cytomegalovirus.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of cytomegalovirus vaccine in healthy participants.

Start Date01 Nov 1997

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

100 Clinical Results associated with Cytomegalovirus peptide vaccine(City of Hope National Medical Center)

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100 Translational Medicine associated with Cytomegalovirus peptide vaccine(City of Hope National Medical Center)

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100 Patents (Medical) associated with Cytomegalovirus peptide vaccine(City of Hope National Medical Center)

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3

Literatures (Medical) associated with Cytomegalovirus peptide vaccine(City of Hope National Medical Center)

01 Apr 2019·Biology of Blood and Marrow TransplantationQ2 · MEDICINE

Rapid Acquisition of Cytomegalovirus-Specific T Cells with a Differentiated Phenotype, in Nonviremic Hematopoietic Stem Transplant Recipients Vaccinated with CMVPepVax

Q2 · MEDICINE

Article

Author: Longmate, Jeffrey ; Zhou, Qiao ; La Rosa, Corinna ; Aldoss, Ibrahim ; Hardwick, Nicola ; Diamond, Don J ; Kaltcheva, Teodora ; Nakamura, Ryotaro ; Lingaraju, Chetan Raj

Early cytomegalovirus (CMV) reactivation remains a significant cause of morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients. CMVPepVax is an investigational peptide vaccine designed to control CMV infection in HCT recipients seropositive for CMV by stimulating the expansion of T cell subsets that target the CMV tegument protein pp65. In a randomized Phase Ib pilot trial (ClinicalTrials.gov NCT01588015), two injections of CMVPepVax (at days 28 and 56 post-HCT) demonstrated safety, immunogenicity, increased relapse-free survival, and reduced CMV reactivation and use of antivirals. In the present study, we assessed the phenotypes and time courses of the pp65-specific CD8 T cell subsets that expanded in response to CMVPepVax vaccination. The functionality and antiviral role of CMV-specific T cells have been linked to immune reconstitution profiles characterized predominantly by differentiated effector memory T (TEM) subsets that have lost membrane expression of the costimulatory molecule CD28 and often reexpress the RA isoform of CD45 (TEMRA). Major histocompatibility complex class I pp65₄₉₅_-₅₀₃ multimers, as well as CD28 and CD45 memory markers, were used to detect immune reconstitution in blood specimens from HCT recipients enrolled in the Phase Ib clinical trial. Specimens from the 10 (out of 18) vaccinated patients who had adequate (≥.2%) multimer binding to allow for memory analysis showed highly differentiated TEM and TEMRA phenotypes for pp65_495-503-specific CD8 T cells during the first 100days post-transplantation. In particular, by day 70, during the period of highest risk for CMV reactivation, combined TEM and TEMRA phenotypes constituted a median of 90% of pp65_495-503-specific CD8 T cells in these vaccinated patients. CMV viremia was not detectable in the patients who received CMVPepVax, although their pp65_495-503-specific CD8 T cell profiles were strikingly similar to those observed in viremic patients who did not receive the vaccine. Collectively, our findings indicate that in the absence of clinically relevant viremia, CMVPepVax reconstituted significant levels of differentiated pp65_495-503-specific CD8 TEMs early post-HCT. Our data indicate that the rapid reconstitution of CMV-specific T cells with marked levels of effector phenotypes may have been key to the favorable outcomes of the CMVPepVax clinical trial.

01 Feb 2016·The Lancet HaematologyQ1 · MEDICINE

Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial

Q1 · MEDICINE

Article

Author: Farol, Len ; Snyder, David S ; Drake, Jennifer ; Cai, Ji-Lian ; Forman, Stephen J ; La Rosa, Corinna ; Diamond, Don J ; Zhou, Qiao ; Aldoss, Ibrahim ; Lampa, Melanie G ; Slape, Cynthia ; Salhotra, Amandeep ; Nakamura, Ryotaro ; Longmate, Jeffrey ; Zaia, John A ; O'Donnell, Margaret ; Miller, Jeffrey S

BACKGROUNDPatients seropositive for cytomegalovirus (CMV) and undergoing allogeneic haemopoietic stem-cell transplantation (HCT) are at risk for CMV reactivation. Stimulating viral immunity by vaccination might achieve CMV viraemia control without the need for antiviral agents. CMVPepVax is a chimeric peptide composed of a cytotoxic CD8 T-cell epitope from CMV pp65 and a tetanus T-helper epitope. It is formulated with the adjuvant PF03512676, a Toll-like receptor 9 agonist, which augments cellular immunity. We aimed to assess safety, immunogenicity, and possible clinical benefit of the CMVPepVax vaccine in patients undergoing HCT.METHODSWe did a randomised, open-label, phase 1b trial at one transplant centre in the USA. Eligible patients were CMV-seropositive, positive for HLA-A*0201, aged 18-75 years, and undergoing HCT from a matched-related or matched-unrelated donor. Patients were reassessed for eligibility on day 28 after HCT. We randomly allocated patients to either the CMVPepVax vaccine or observation, in blocks stratified by CMV donor serostatus. CMVPepVax was administered subcutaneously on days 28 and 56. The primary outcome was safety, which consisted of secondary graft failure, grade III-IV acute GVHD, non-relapse mortality by day 100, serious adverse events related to the vaccine (judged by the data and safety monitoring committee [DSMC]) grade 3-4 adverse events related to the vaccine (judged by the DSMC) within 2 weeks of vaccination, and development of double-strand (ds) DNA autoantibodies. Statistical analyses included all randomised patients and were done per-protocol. This study is registered with ClinicalTrials.gov, number NCT01588015. This trial is closed to accrual and the final analysis is presented in this report.FINDINGSBetween Oct 31, 2012, and Nov 5, 2014, 36 eligible patients were allocated to either CMVPepVax (n=18) or observation (n=18), with no adverse effect on HCT (no secondary graft failures in either group) or cases of acute GVHD (seven patients assigned vaccine and six under observation had acute GVHD of grade 2 or less), and no unexpected adverse events. Compared with observation, better relapse-free survival was recorded in patients allocated the vaccine (seven vs one; hazard ratio [HR] 0·12, 95% CI 0·01-0·94; p=0·015). No patients had non-relapse mortality by day 100. One serious adverse event (grade 1 fever) was attributed to CMVPepVax but resolved within 48 h. Four patients assigned the vaccine had a serious adverse event, which was unrelated to the vaccine (grade 3 thrombocytopenia, grade 3 device-related infection, grade 2 nausea, and grade 1 fever), compared with nine patients under observation (grade 4 maculopapular rash, grade 3 nausea, grade 3 infection, grade 3 thrombotic thrombocytopenic purpurea, grade 2 nausea, grade 2 generalised muscle weakness, grade 2 infection, grade 1 fever, and grade 1 fatigue; p=0·16). 54 grade 3-4 adverse events were reported in patients assigned the vaccine compared with 91 in patients who were under observation (p=0·2). No patients had grade III-IV acute GVHD or developed dsDNA autoantibodies.INTERPRETATIONThe results show safety and immunogenicity of the CMVPepVax vaccine. The prospect of substantial clinical benefits warrant testing in a phase 2 trial.FUNDINGNational Cancer Institute.

01 May 2004·Human ImmunologyQ4 · MEDICINE

Progress made towards the development of a CMV peptide vaccine

Q4 · MEDICINE

Review

Author: S.J Paston ; I.A Dodi ; J.A Madrigal

Cytomegalovirus disease still remains a major cause of morbidity and mortality in hematopoietic stem cell transplantation recipients. The cell-mediated immune response is essential in the maintenance of latency and the resolution of primary infections. The identification of immunodominant cytomegalovirus antigens has enabled researchers to determine the best candidate antigens to be included in a cytomegalovirus vaccine. Such a vaccine would have to stimulate both a cell-mediated and humoral immune response. Recent advances have enabled the rapid identification of minimal cytotoxic epitopes required to trigger such responses. Epitope mapping to date has mainly focused on the pp65 antigen but other antigens such as IE1 are starting to be mapped. A human leukocyte antigen allele hierarchy is starting to emerge that is dependent on the alleles present in an individual; this is relevant when considering what peptides should be included in a vaccine. This review looks at the current methods available for epitope mapping and the progress that has been made to date.

100 Deals associated with Cytomegalovirus peptide vaccine(City of Hope National Medical Center)

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cytomegalovirus Infections	Phase 3	-	University of Minnesota	-
Adult Acute Myeloblastic Leukemia	Phase 2	United States	City of Hope National Medical Center	21 May 2015
Adult Acute Myeloblastic Leukemia	Phase 2	United States	National Cancer Institute	21 May 2015
Aggressive-Phase Chronic Myelocytic Leukemia	Phase 2	United States	National Cancer Institute	21 May 2015
Myelodysplastic Syndromes	Phase 2	United States	City of Hope National Medical Center	21 May 2015
Myelodysplastic Syndromes	Phase 2	United States	National Cancer Institute	21 May 2015
Myelofibrosis	Phase 2	United States	City of Hope National Medical Center	21 May 2015
Myelofibrosis	Phase 2	United States	National Cancer Institute	21 May 2015
Myeloproliferative Disorders	Phase 2	United States	National Cancer Institute	21 May 2015
Myeloproliferative Disorders	Phase 2	United States	City of Hope National Medical Center	21 May 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02396134 (CTgov)	Phase 2	Hodgkin's Lymphoma \| Chronic phase chronic myeloid leukemia \| Chronic Lymphocytic Leukemia \| Adult Acute Myeloblastic Leukemia \| Cytomegalovirus Infections \| Myeloproliferative Disorders \| Adult Acute Lymphocytic Leukemia \| Aggressive-Phase Chronic Myelocytic Leukemia \| Multiple Myeloma \| Myelofibrosis \| Non-Hodgkin Lymphoma \| Myelodysplastic Syndromes \| Adult Lymphoblastic Lymphoma	61	Laboratory Biomarker Analysis+CMVpp65-A0201 peptide vaccine (Arm I (CMVpp65-A0201 Peptide Vaccine))	vnecmbzaoi(mhhcbhaivr) = jdtobxtmhh dhjhfzrlnk (tuwugbygiq, iffpprofph - qubciebuco) View more	-	12 Jul 2023
				Placebo (Arm II (Placebo))	vnecmbzaoi(mhhcbhaivr) = xepsejrwaq dhjhfzrlnk (tuwugbygiq, pehlzxvjdf - textoctvep) View more
NCT02396134 (ASH 12021 \| ASH 22021) Manual	Phase 2	Cytomegalovirus Infections	61	Cmvpepvax	alqtcejsma(lnklnwdbju) = rtpdliqeit ictrllwpep (vjryrwoqbv )	Negative	05 Nov 2021
				Placebo	alqtcejsma(lnklnwdbju) = ljemoxvisq ictrllwpep (vjryrwoqbv )
Tandem Meetings ASTCT and CIBMTR2019	Not Applicable	Hematopoietic stem cell transplantation	-	CMVPepVax	kmondpnkuc(eynmioujsu) = jhwzatsmjt femfomhvxz (inlqblngar )	-	01 Mar 2019