PMID- 18077621
OWN - NLM
STAT- MEDLINE
DCOM- 20080311
LR  - 20211020
IS  - 1556-679X (Electronic)
IS  - 1556-6811 (Print)
IS  - 1556-679X (Linking)
VI  - 15
IP  - 2
DP  - 2008 Feb
TI  - Peptide impurities in commercial synthetic peptides and their implications for 
      vaccine trial assessment.
PG  - 267-76
AB  - The advent of T-cell assay methodologies that are amenable to high throughput 
      coupled with the availability of large libraries of overlapping peptides have 
      revolutionized the fields of vaccine efficacy testing and cellular immune 
      response assessment. Since T-cell assay performance is critically dependent upon 
      the quality and specificity of the stimulating peptides, assurance of 
      high-quality and reliable input peptides is an important aspect of assay 
      validation. Herein, we demonstrate that individual peptides from large human 
      immunodeficiency virus (HIV)-based peptide library sets obtained directly from 
      two independent custom peptide suppliers contained contaminating peptides capable 
      of giving false-positive results, which were consistent with nominal 
      antigen-specific CD8+ T-cell responses. In-depth investigation of the cellular 
      response in terms of responding CD8+ T-cell frequency and human leukocyte antigen 
      (HLA) restriction led to the conclusion that one set of HIV type 1 
      (HIV-1)-derived peptides was contaminated with a peptide from human 
      cytomegalovirus (HCMV), which is commonly used in cellular immunology research 
      applications. Analytical characterization of the original stock of the suspect 
      HIV-1 peptide confirmed the presence of approximately 1% by weight of the HCMV 
      peptide. These observations have critical implications for quality assurance (QA) 
      and quality control (QC) of peptides used in clinical trials where cellular 
      immune-based assays are important end-point determinants. We propose a simple 
      schema of biological QA/QC protocols to augment the standard biochemical QA/QC 
      analyses as a means to circumvent this and other problems that can affect 
      cellular immune-based assay outcome and interpretation.
FAU - Currier, Jeffrey R
AU  - Currier JR
AD  - U.S. Military HIV Research Program, Rockville, Maryland 20850, USA. 
      jcurrier@hivresearch.org
FAU - Galley, Lynee M
AU  - Galley LM
FAU - Wenschuh, Holger
AU  - Wenschuh H
FAU - Morafo, Vivian
AU  - Morafo V
FAU - Ratto-Kim, Silvia
AU  - Ratto-Kim S
FAU - Gray, Clive M
AU  - Gray CM
FAU - Maboko, Leonard
AU  - Maboko L
FAU - Hoelscher, Michael
AU  - Hoelscher M
FAU - Marovich, Mary A
AU  - Marovich MA
FAU - Cox, Josephine H
AU  - Cox JH
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071212
PL  - United States
TA  - Clin Vaccine Immunol
JT  - Clinical and vaccine immunology : CVI
JID - 101252125
RN  - 0 (AIDS Vaccines)
RN  - 0 (Peptide Library)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - AIDS Vaccines/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Clinical Laboratory Techniques/*standards
MH  - Cytomegalovirus/chemistry
MH  - *Drug Contamination
MH  - HIV
MH  - HIV-1/*immunology
MH  - Humans
MH  - *Peptide Library
MH  - Quality Assurance, Health Care
MH  - Quality Control
MH  - Viral Proteins/analysis
PMC - PMC2238048
EDAT- 2007/12/14 09:00
MHDA- 2008/03/12 09:00
PMCR- 2008/08/01
CRDT- 2007/12/14 09:00
PHST- 2007/12/14 09:00 [pubmed]
PHST- 2008/03/12 09:00 [medline]
PHST- 2007/12/14 09:00 [entrez]
PHST- 2008/08/01 00:00 [pmc-release]
AID - CVI.00284-07 [pii]
AID - 0284-07 [pii]
AID - 10.1128/CVI.00284-07 [doi]
PST - ppublish
SO  - Clin Vaccine Immunol. 2008 Feb;15(2):267-76. doi: 10.1128/CVI.00284-07. Epub 2007 
      Dec 12.