title: Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.
abstract: In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 μg per peptide dose, the 50 μg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50% at the 50 μg dose (7 of 14) and 100 μg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened.
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 502, Little Rock, Arkansas, 72205, USA.
authors.forename: Hannah N
authors.initials: HN
authors.lastname: Coleman
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Greenfield
authors.affiliation: Translational Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Stratton
authors.affiliation: Translational Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Vaughn
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 502, Little Rock, Arkansas, 72205, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kieber
authors.affiliation: Department of Dermatology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Moerman-Herzog
authors.affiliation: Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Horace J
authors.initials: HJ
authors.lastname: Spencer
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Wilbur C
authors.initials: WC
authors.lastname: Hitt
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 502, Little Rock, Arkansas, 72205, USA.
authors.forename: Charles Matthew
authors.initials: CM
authors.lastname: Quick
authors.affiliation: Department of Medicine, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Hutchins
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.|Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Ricky D
authors.initials: RD
authors.lastname: Edmondson
authors.affiliation: Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Erickson
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 502, Little Rock, Arkansas, 72205, USA. mnakagawa@uams.edu.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D053719:Tandem Mass Spectrometry; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020543:Proteome; D022223:Vaccines, Subunit
keywords: Cervical intraepithelial neoplasia; Clinical trial; HPV; T cells; Therapeutic vaccine; Viral load